This book explores the new applications of established theories or adapts theoretical approaches in order to illuminate behaviour in the field of food. It focuses on social processes at the downstream end of the food chain, processes of distribution and consumption. The book reviews the existing disciplinary approaches to understanding judgements about food taste. It suggests that the quality 'halal' is the result of a social and economic consensus between the different generations and cultures of migrant Muslims as distinct from the non-Muslim majority. Food quality is to be viewed in terms of emergent cognitive paradigms sustained within food product networks that encompass a wide range of social actors with a wide variety of intermediaries, professional and governmental. The creation of the Food Standards Agency (FSA) and the European Food Safety Authority (EFSA) occurred at a juncture when perceptions of policy failure were acknowledged at United Kingdom and European Union governmental levels. The book presents a case study of retailer-led food governance in the UK to examine how different 'quality logics' actually collide in the competitive world of food consumption and production. It argues that concerns around food safety were provoked by the emergence of a new food aesthetic based on 'relationalism' and 'embeddedness'. The book also argues that the study of the arguments and discourses deployed to criticise or otherwise qualify consumption is important to the political morality of consumption.
In this chapter, we explore how the promise and the work of personalised cancer medicine has evolved as genomic medicine has advanced. We trace some of the forms of value this has generated for patients and practitioners, industry and economies, and set the scene for our wider exploration of how this kind of future-crafting is reshaping the roles and responsibilities of cancer patients and practitioners. Drawing on a range of social scientific literatures and studies on genomic medicine for cancer, together with data from our own case studies, we discuss how patients and their families are enrolled in cancer-related genomic medicine, not just as end-users, but as co-producers of genomic knowledge and technologies. We consider how this, in turn, enacts personal and collective futures where cancer, if not cured, will be held at bay by molecular monitoring and tailored treatments.
Throughout we try to shine a light on how patients as service users, research participants, representatives, advocates, campaigners and supporters of fellow patients as well as their carers, families and friends enact, query and transform promissory visions and agendas for personalised, predictive and preventative cancer medicine through different kinds of participation (and non-participation). We trace how patients and their families engage with personalised genomic medicine for cancer through various kinds of clinical and other encounters and partnerships. We explore co-production and efforts to ‘empower patients, researchers and providers to work together toward development of individualised care’ in the words of the mission statement of the US NIH Precision Medicine initiative, 1 and trace the kinds of participation involved in ‘participatory medicine’ (Hood and Auffray 2013). As Prainsack (2017) notes, the emphasis is on patients driving these new agendas, inviting them to generate data and push the boundaries of research and care. Drawing on Adams et al.'s discussion of anticipation and futures, it appears that personalised medicine ‘mobilizes everything and everyone’, aiming for certainty but working in a context of the ‘ever changing nature of truth’ (2009: 256, 246).
One key area of consideration is patients’ involvement in novel kinds of adaptive clinical trials that create moral, epistemic and commercial value through the continual negotiation of best possible futures for patients as individuals and as a collective (Montgomery 2017a; 2017b ). We investigate the rise of ‘experimental patients’ in molecular oncology; patients who are actively involved in crafting treatment regimes together with healthcare professionals, including as research participants. We will also explore how patients, including potential and past patients, together with others affected by cancer in their families, act as advocates for personalised genomic medicine, particularly in relation to access to trials and costly experimental drugs, as part of these anticipatory regimes (Adams et al. 2009). Although regulatory and healthcare systems are adapting to accommodate these novel interventions, concerns about access as well as cost-effectiveness have kept the issue of cancer drugs firmly on political and personal agendas. What kinds of collective and individual actions does this bring for cancer patients and their families seeking access to novel therapies or diagnostics? How does this perform hope and anticipation about the future of personalised medicine? What kind of value does this produce and for whom?
One of the difficulties with reviewing the evolution of personalised genomic medicine for cancer is knowing where to start. Rooting the ‘origin’ of personalised medicine in the development of targeted therapies such as Gleevec or Herceptin foregrounds one set of technologies at the expense of other kinds of research and innovation and other kinds of practices and actors involved in these processes. The risk of a potted or so-called ‘Whig’ history of personalised genomic medicine for cancer is that it replicates the kinds of narratives we need to examine critically. We can think of this as the ‘magic bullet’ discourse – where a particular drug is given pride of place as the new cure for disease and stories are written about the heroic scientists and doctors involved in its development – a common cultural trope that can be found across policy, professional and patient accounts. To avoid replicating this, we try to offer a set of reflections on interlinked social and technological developments that form part of the story of personalised genomic medicine for cancer. We have ordered this into sections and tried to give a sense of chronology for ease of reading, but we would like to stress that we have not ranked these sections by importance. We adopt the same approach for the remainder of the book which looks more closely at a series of case studies of personalised genomic medicine for cancer.
We have also tried to exercise caution around claims to novelty. Although we can see the transformative nature of current initiatives that are driving new practices, collaborations and partnerships, we must remember that personalised medicine is not entirely new. Clinical practice has always made adjustments, for example to dosages based on the individual characteristics of patients: one size has never fitted all, even with much evidence-based medicine being driven by standard protocols (Longo 2013). So we must take care to appreciate personalised medicine as a ‘rhetorical entity’ (Van Lente and Rip 1998), used by actors from industry, government, regulation, academia, patient advocacy and clinical practice ‘to not only describe a future state but to bring it into being’ (Tutton 2012: 1721). Approaching innovation as a series of incremental shifts and reassemblages of genomic and other data, together with wider agendas of personalisation and participation, we need to attend to ideas of patient centredness, shared decision making, patient involvement and empowerment (Mead and Bower 2000; Greenhalgh 2009), as well as the integration of genomic information with an increasingly wide range of clinical, social and personal information.
Targeted treatments: a start to the story of personalised genomic medicine for cancer
Cancer came to be understood as a genetic disease in the 1980s when immunochemistry researchers began to coalesce around the so-called oncogene paradigm, approaching cancer as a subcellular disease to be treated by interfering with biochemical processes within, between and on cell surfaces. Focusing on the role of somatic, as opposed to germline (inherited), genetic mutations in stimulating the excessive growth and division of cells which formed tumours, researchers identified candidate mutations and studied the expression of proteins in patients to identify subgroups of patients with these particular genetic variations. Attention turned to blocking the action of these genes through drugs – monoclonal antibodies. These act on the genetic signalling pathway to inhibit the production of specific proteins that encourage tumour growth. What was once understood as one type of cancer became subdivided into several different subtypes (Yeo and Guan 2017). Through these developments, biomarker testing and treatment became entwined in so-called ‘theragnostics’, shifting the process of regulatory approval to accommodate the integration of testing technologies into treatment decisions and provisions (Fujimura 1996; Morange 1997; van Helvoort 1999; Keating and Cambrosio 2011).
As efforts intensified to identify more and more mutations with potentially actionable (druggable) pathways and to test this through ever more complex clinical trials, patients’ participation in research grew. Of course, there is a long track record of patients being part of experiments in cancer medicine, but we see a shift in the scale and promise of experimentation developing over this period, as many more kinds of subtypes and targeted therapies emerged to be tried in combination (DeVita and Chu 2008; Keating and Cambrosio 2011; Jain 2013). Research became almost routinised in contemporary cancer care.
The molecular turn in cancer has deep and complex roots, but there are two paradigmatic cases that are frequently invoked as part of its history: Gleevec and Herceptin. Through telling and retelling these stories, the possibilities of personalised genomic medicine for cancer are reproduced, generating support for medical research and more permissive regulation to facilitate more of these kinds of ‘wins’. Patients form an important part of these accounts, collectively and individually, as we now go on to explore.
Although Herceptin is the best-known case of early targeted therapies for cancer, scientists and social scientists have argued that it is actually imatinib (Gleevec), a small molecule that interferes with molecular pathways in chronic myeloid leukemia (CML), that is closer to a paradigm case. As Keating and Cambrosio have documented in the in-depth analysis in their book Cancer on Trial, Gleevec, as one of the early targeted therapies granted approval, ushered in a ‘new era of therapeutic agents produced using the tools of molecular biology’ (2011: 303). This development was considered revolutionary: Dan Vasella, the CEO of Novartis, the manufacturers, called his co-authored book about the drug Magic cancer bullet: how a tiny orange pill is rewriting medical history (Vasella and Slater 2003).
Yet, as Keating and Cambrosio (2011) demonstrate, the transformative nature of Gleevec was not just a matter of molecular pathways, but of research and regulatory processes. The trial phases proceeded rapidly and involved higher numbers of patients than usual because of a demand for participation in the context of the hope of a cure. Participants on Phase 1 trials had typically failed standard therapy but were nevertheless considered healthy enough to withstand the trial. The results were described as remarkable, with the vast majority of patients who received doses greater than 300mg going into complete remission. But there was a catch: remission was linked to continued use, thereby transforming CML into a more manageable, longer-term condition.
Phase 2 trials followed from the initial success at Phase 1 and involved high numbers of participants, achieved in part through developing an international network of trial sites and the continued involvement of Novartis in trial audit and review. Patients, too, had a role in ensuring that such research took place via the involvement of patient groups and activists. Keating and Cambrosio (2011) note that a patient petition supporting the trial was launched on the internet by a Montreal CML patient, gathering 3,000 signatures within a matter of weeks. Novartis reported receiving many letters and phone calls from patients, and their relatives, seeking access to the drug.
Subsequent Gleevec trials also saw the same kind of active patienthood, including what Keating and Cambrosio call ‘epistemological activism’ (2011: 340). They give the example of patients with rare gastrointestinal tumours (GIST) who organised a patient group called the Life Raft Group. Because some GIST patients had been found to be responsive to Gleevec, this kind of public patienthood focused on sharing information on trials and data on side-effects and performance. As personalised genomic medicine for cancer developed, these new kinds of patient collectives gained an increasing foothold in institutional practices such as data monitoring committees, as well as co-hosting meetings of various cancer stakeholders, in what authors such as Callon and Rabeharisoa (2008) have described as hybrid research collectives.
Gleevec was approved rapidly by the US Food and Drug Administration (FDA), less than four years after the first human dose. Its success and promise caused regulatory processes to speed up to accommodate similar innovations. Alongside these novel regulatory, partnership and trial arrangements, Gleevec also introduced a new pricing structure which saw a departure from so-called blockbuster drugs to the provision of stratified, higher-priced medicines for smaller groups of patients, so-called ‘niche-busters’ (Keating and Cambrosio 2011: 319).
As the GIST example illustrates, the approach taken with Gleevec is also being used for other cancers with similar molecular anomalies (Rajan 2006; Madhu 2017). Keating and Cambrosio (2011) note that these processes of redefinition were achieved in part via a proliferation of trials. By 2002 Gleevec had been part of over forty trials for a range of cancers sharing common molecular abnormalities. Gleevec also spawned a range of drug innovations. Given that a small number of patients can develop resistance to the drug, and changing the dose does not always help to manage this, this required patients to switch to other therapies. This introduces a ‘proliferation of targeted agents aimed at similar pathways or receptors [which] may transform the oncology drug market’ (Keating and Cambrosio 2011: 327).
Gleevec is now an established part of treatment for CML and other cancers such as gastrointestinal tumours. Patients and practitioners have come to experience some of these cancers as chronic and treatable because of these molecular actors, further motivating the promissory discourses of personalisation and cure. One of our interviewees, Andrew, who had acute myeloid leukemia, described his leukemia as a group of terrorists being fought by the British Army, with Mylotarg (a targeted therapy) described as a ‘sniper’, able to target abnormal cells with greater precision: ‘It's actually very encouraging, it's very personalised and you think, this isn't just generic, this is to give me as an individual person the best chance of survival here.’ However, other patients, who have been on targeted treatments long term, were less invested in the promise of personalisation as their treatment regimes, and indeed their cancer, became unremarkable in their everyday lives. Although one person who was on Gleevec long term considered himself ‘lucky to have had that type of cancer’, and to be treated with targeted therapy to which he ‘responded very well’, he also described feeling like a ‘fraud’ because of the treatment's success: ‘When people say, “how's your leukemia?” it's almost like I'd forgotten I'd got it.’ Others with blood cancers we interviewed were more anxious around the personalisation of treatment, expressing concern about resources. For example, one of our interviewees, Bianca, had been diagnosed with AML eighteen months prior to her interview, and had been referred urgently for treatment due to the severity of her condition. She described having a ‘weird’ leukemia profile, showing both a ‘good’ and ‘bad profile’ in terms of her chances of staying in remission following chemotherapy. This provoked uncertainty about her treatment plan, with the eventual decision that she undergo several rounds of chemotherapy to ‘get her into remission’, followed by a stem cell transplant. Bianca elaborated her mixed feelings about personalised treatment:
I suppose in a way it gives you confidence that the treatment you're getting is as personal and appropriate for you … but … it's also a little bit kind of worrying, because you think … if all kinds of leukaemia were exactly the same would … the ability to deal with leukaemia and have a good prognosis be higher if they were only, if there was only one brand of leukemia and you could focus everything on that, then would the outcomes improve, or because all these different brands exist and you've got to spend time dealing with all these different brands, does that mean eventual outcomes are going to be lower because resources are being spread more widely?
As this excerpt demonstrates, personalised genomic medicine sparks a range of responses from patients, from positivity to anxieties about the meanings and implications of personalisation for one's own treatment, for other patients with different profiles and about access to treatment more generally. Making sense of these various options and their implications involves patients and their families in emotional labour, working with anxiety, as well as a sense of good fortune and gratitude.
Practitioners in this field also spoke of the complex negotiation of the different kinds of treatment and research opportunities that characterised their work with patients, an ongoing process of optimisation of treatment for patients as individuals and of developing yet more personalised regimens for future patients as part of a wider bioeconomy. This involved moving between different registers of anticipation and promise, as captured in the excerpt from a senior haematologist below:
there's a drug we use here called Ibrutinib which is a so called BTK inhibitor and that blocks or counteracts the effect of a particular mutation in leukemia cells. And in some people that works brilliantly. But you can have a mutation in another gene called CARD11 which quite commonly occurs in association with it and it just doesn't work at all … The very first precision medicine was a type of leukemia, a drug called imatinib [Gleevec], and that worked fantastically well. And when I started off everybody who acquired myeloid leukemia died within about three or four years, and now virtually nobody dies of chronic myeloid leukemia. Now imatinib cost thirty thousand a year per patient for life, and we're going from – there's twenty-five new patients in the region a year but there's now something like five hundred people on active treatment (laughs) … And that's just for one very rare cancer … So there's a big economic argument here for only giving these drugs to people where it will work. But obviously the pharma companies would rather it was given to everybody (laughs). So it opens up a whole lot of areas like that as well. But at the clinical level, a lot of clinicians and patients would rather not know this, they would rather have the drug and see if it works rather than have an upfront prediction.
Here we see an account of a future of tailored medicine optimised to treat only patients who will benefit sitting alongside other accounts of tensions between providers and pharma and of patients and clinicians wanting to maintain uncertainty. This preserves a sense that their chances of success are being optimised – key themes that we will explore further throughout the book. At the same time, practitioners were also concerned about the proliferation of cancer subtypes and research activity in the blood cancer area, giving them a sense that they lacked specialisation and the capacity to deliver personalisation in a complex, ever-changing field, another key tension in our research. For example, two haematology nurses we talked with noted that the vast range of conditions meant that they are learning all the time and cannot become ‘too specialised’ when compared with colleagues in breast cancer care. Negotiating professional status and expertise was an integral part of delivering these new opportunities and future possibilities for patients.
Patients are part of the Gleevec story as research subjects, advocates and beneficiaries, but as our own research demonstrates, their experiences of personalised treatments are more wide ranging and complex than the optimistic stories of magic bullets or even epistemological activism might suggest. We can identify similar patterns with Herceptin, arguably an even better-known exemplar of transformative personalisation, as we now go on to discuss.
Herceptin's story is a key part of the success narrative of personalised cancer medicine, eclipsing Gleevec in the public imaginary, not least because of the gender health politics surrounding breast cancer research and care (see Hedgecoe 2004; Abelson and Collins 2009; Keating and Cambrosio 2011). It was developed after scientists at the National Cancer Institute in the US found that a mutation in HER2 (Human Epidermal Growth Factor Receptor 2) could cause normal cells to grow uncontrollably and that the gene's protein was over-expressed in around 30 per cent of breast cancers. It was subsequently shown that an antibody specific to HER2 could slow the growth of breast cancer cells in the laboratory. University scientists went on to collaborate with Genetech, a company that is widely regarded as the pioneer of biotechnology, to develop a HER2-specific antibody called Trastuzumab (Herceptin). In the 1990s, trials of Herceptin, in combination with chemotherapy for patients with metastatic cancers, showed positive outcomes, increasing the median survival rate for patients on a combination of Herceptin and chemotherapy by five months as compared with patients on chemotherapy alone. It was first licensed by the FDA in 1998, for use in patients with metastatic breast cancer, and subsequently approved in the UK in 2002. Use was extended quite quickly, from a treatment for metastatic breast cancer (on its own or in combination with a specific chemotherapy, paclitaxel) to a treatment for early-stage breast cancer. Roche, which acquired a major stake in Genetech in 1990, successfully sought to extend Herceptin's licence to include early-stage breast cancers, and in 2006 the FDA licensed the drug for use with a combination of chemotherapies (doxorubicin, cyclophosphamide and paclitaxel) as an adjuvant treatment for patients with early-stage (localised) HER2 positive breast cancer after surgery. Herceptin became Roche's fifth highest-selling drug by 2002 (Hedgecoe 2004), worth £460 million, and led to a 20 per cent increase in Genetech profits. Herceptin also heralded the ‘package’ approach to test/treatment that persists today. Roche funded HER2 tests before the drug was approved, thus ensuring that it became embedded in oncology practice, preparing a pathway for the drug once it was approved.
As with Gleevec, patients feature in the story of Herceptin as advocates, especially as lobbyists for extending the licence of this treatment to early-stage breast cancer via a concerted media campaign. There is a strong history of advocacy among breast cancer patients, including grassroots movements such as Breast Cancer Action in San Francisco Bay in the US (Klawiter 2004) through to large-scale commercially funded breast cancer awareness campaigns (Sulik 2014). This kind of advocacy presaged a more institutionalised role for patient involvement as well as contributing to the high profiles of breast cancer and breast cancer experience that have shaped public discourse of cancer, including around survivorship, access to drugs and prevention and early detection.
Abraham (2009) highlights the alliances with patients and patient organisations that were involved in the promissory agendas around Herceptin, noting that Roche reputedly engaged public relations companies to encourage women to campaign for access to the drug, including in the NHS in the UK, in so doing constituting its own version of engaged and optimistic patienthood. A 2006 BBC report by Sanchia Berg 2 described the experience of the late Professor Lisa Jardine, professor of history, public intellectual and former chair of the Human Fertilisation and Embryology Authority, who was contacted on behalf of Roche to assist with her accessing Herceptin prior to NICE approval. Although Jardine was reportedly alarmed by this PR exercise and did not enter into an arrangement with Roche, the report noted a number of cases covered in the national media of women who had early-stage breast cancer and whose Primary Care Trust (PCT) had refused funding for Herceptin, with the emphasis on trying to ‘shame’ trusts into funding the treatment. Herceptin, and the associated test for HER2, was subsequently approved by NICE for early-stage breast cancer, but questions were asked about the involvement of Roche in these media cases and about the speed of the decision, which appeared to be rushed according to some commentators in the Berg report, including Dr Richard Horton, the editor of The Lancet.
Supportive press coverage featuring patient testimony is a feature of these campaigns for extended access. In a comparative analysis of UK and Canadian coverage of Herceptin, Abelson and Collins (2009) found that reporters presented individualistic perspectives on access to Herceptin as highly beneficial. This is echoed in a paper on the New Zealand context by Gabe et al., in which they describe coverage as being dominated by ‘personal stories drawing on the news frame of “desperate, sick women in double jeopardy because of callous government/incompetent bureaucracy”’ (Gabe et al. 2012: 2358, quoting MacKenzie et al. 2008: 305). As Gabe et al. (2012) note, press coverage is shaped by press releases from companies and, in the case of Herceptin, Roche used this route effectively as part of its campaign for approvals. For example, a Roche press release covering the interim results of trials of Herceptin in early-stage breast cancers, apparently timed to coincide with the American Society for Clinical Oncology meeting in June 2005, noted that ‘women with early stage HER-2 positive breast cancer reduced their risk of their cancer returning by 46 percent when using the targeted therapy Herceptin’ (Gabe et al. 2012: 2355, quoting Roche press release). 3 Patient narratives, while providing a window on to the experience of cancer and all its hardships, can also be deployed strategically by pharma to garner support and demand. Indeed, individual cases and stories fit well with the individualising paradigm of personalised, precision medicine, providing authenticity through personal experience and individual successes and efforts. But patient groups can become assimilated in other kinds of campaigns too. Gabe et al. discuss the example of the Breast Cancer Advocacy Association in New Zealand, which lobbied regulators and government to improve access, including supporting a 2008 court case by a group of ‘Herceptin Heroes’ which resulted in the regulator having to conduct further consultation to formulate policy. Through these practices the side-effects of drugs such as Herceptin, which include, among others, cardiac toxicity, are downplayed in favour of its promise of longer lives for patients.
As with Gleevec, new multinational consortia were developed to establish viable trials for the drug. HERA (HERceptin Adjuvant) was initially run by the not-for-profit Breast International Group, established in 1996 and supported by Roche. As Keating and Cambrosio (2011) discuss, this ‘consortia of consortia’ encompassed numerous groups, hospitals, laboratories and centres, together with a patient organization, Europa Donna, which were represented on the trial committee. The complex arrangements for data governance and trial management, designed to maintain ‘scientific independence’ from industry, led to tensions with Roche, and careful configuration of data monitoring committees was required to maintain their collaboration (Keating and Cambrosio 2011: 329). The ‘molecular turn’ challenged a trial methodology already under strain as patients and clinicians sought out novel treatments and changed assessment criteria to demonstrate therapeutic benefit. Later trials designed to assess the efficacy of Herceptin also ran into difficulty as clinicians were reluctant to assign patients to the option when Herceptin was discontinued.
It is well established that clinicians and scientists worked closely with the manufacturer of Herceptin to gain approval for the drug through research trials and other studies. Gabe et al. (2012; see also Busfield 2006; Light 2010) give an example of this kind of co-production, which features a review of Herceptin in the clinical setting by breast cancer researchers from Guy's and St Thomas's Hospital, London (Miles 2001). Although the author acknowledged support from industry, including Roche, Gabe et al. (2012) note that industry support is not mentioned in other papers, including a supportive review of recent trials, methods of HER2 testing and the combination use of Herceptin.
Patienthood in media and corporate narratives of Herceptin is framed in familiar registers of hope and despair. But as other social research demonstrates, the take-up of Herceptin, and patients’ and practitioners’ roles therein, was more complex and their attitudes were more ambivalent than these versions of patienthood suggest. Even though HER2 was one of only several targetable mutations where there was consensus about its predictive and prognostic value (it is now a routine test for invasive breast cancer in the UK), professionals were wary about the gap between the messy realities of treatment and patient expectations as it was introduced into practice (Tutton and Jamie 2013). Hedgecoe's (2004; 2005 ) detailed work on the development of pharmacogenomics in a UK breast cancer clinic in the 2000s explores these themes. Hedgecoe observed how metastatic breast cancer patients could be tested for HER2, and Herceptin was offered to HER2+ patients (provided free by Roche), but he notes that clinicians did not rush to test but sought to protect patients from information overload. In the words of one of Hedgecoe's interviewees, it is only ‘At the point at which you can do something about it, then it [HER2 testing] becomes more relevant’ (Hedgecoe 2005: 1204). Hedgecoe draws attention to other kinds of clinician ambivalence around HER2 testing in the UK at this time, including in comparison with practice elsewhere, notably the US, where, in 2001, the American Society of Cancer Oncology recommended that HER2 testing be available to every primary breast cancer patient. He links UK clinicians’ reticence to view HER2 as ‘special’ to a general culture of keeping expenses down as compared to other healthcare systems. Clinicians’ concerns about managing patients’ expectations and dealing with disappointments (when HER2 over-expression was not detected and Herceptin was not prescribed) increased their ambivalence about the test.
Patients also experience ambivalence about this kind of testing, even now that it is well established. Although many of the social scientific and popular narratives of Herceptin have focused on the activism for access to the drug in which some patients became involved, this kind of patient activity is not all that being on or accessing Herceptin involves. A particular issue arises here regarding being a HER2+ subtype patient entitled to Herceptin. Breast cancer patients must negotiate these kinds of typologies, and the resultant stratification of treatment experience, with their friends and other people they meet, as the excerpt below from an interview with Jane, in her early fifties, who had had cancer at a relatively young age and was on maintenance medication, illustrates:
There's sort of the public perception is … there is just breast cancer and I thought that, but there isn't, there are very different types and it can be very individual so … that's sometimes quite hard when other people ask you about it, to try to say, well, I didn't have the same thing as your mum.
‘Not being the same’ can introduce anxiety, doubt and concern, given that it can mean not accessing particular or familiar kinds of treatments like others. Another person with breast cancer who we interviewed, Yvette, described how she was offered surgery first, whereas her friend, another breast cancer patient with a popular blog, was receiving neoadjuvant chemotherapy before surgery (the patient pathway for cases of triple negative or HER2+ cancers or for those women with larger tumours [Derks and van de Velde 2018]). This made Yvette wonder ‘why am I not getting that?’; she speculated about whether this was because her friend was receiving private healthcare, telling us that she did not understand ‘how they make those decisions’.
When we delve deeper into experiences of Herceptin and HER2, we find that breast cancer patients and practitioners, like blood cancer patients and practitioners using targeted treatments such as Gleevec, have a range of experiences of personalised genomic medicine for cancer that include, but also go beyond, the roles of enthusiastic research beneficiary or advocate. Patients and practitioners are weaving genomic medicine into their encounters with other patients, relatives, tests and treatments as they navigate their future and that of others. This involves a complexity of values and work, as we go on to explore further below. Here, patienthood begins to multiply as experiences and representations proliferate and diverge, but it also converges in dominant media and corporate tropes of active, engaged and sometimes desperate patients.
Targeted therapies proliferate
The promise of a suite of targeted therapies to give patients and clinicians more options to treat cancers as they resist, mutate and evolve over time is a powerful feature of personalised cancer medicine. As a recent report from the Institute of Cancer Research on improved access to targeted therapies asserts:
Cancer is enormously complex, and it can adapt and evolve in response to changes in its environment – including drug treatment. Only through radical innovation will we deliver the step-change improvements we need in cancer treatment, by attacking cancer in new ways that allow us to overcome or prevent drug resistance. We need to create a wider variety of targeted drugs and immunotherapies and find new treatment combinations that can block cancer's escape routes. 4
Popular culture and everyday talk is replete with personal stories of struggles around access, scientific breakthroughs and big futures of cancer as a chronic, treatable disease. We can trace these narratives across professional, popular and policy literatures, our own observations and interviews, much of which hinge on the idea of the drug as a potent force in the ongoing battle against cancer in both the body and the body politic. In this cultural narrative the next drug is always around the corner; radical innovation becomes routine, as one lung cancer consultant explained in relation to news of a recent approval:
And quite excitingly, just in this week … one of those drugs has just been NICE approved, … as a follow on treatment for patients who've stopped responding to the first tablet. So when you stop responding to the first tablet … instead of having to go and have chemotherapy you can go and have another tablet which … is targeted as well. So that gives you hope that you might then find a third tablet and a fourth tablet when they stop responding to that.
Many patients are already able to access tried and tested therapies such as Gleevec and Herceptin, but for other patients with different kinds of cancer, including lung cancer patients, drugs are more experimental and less readily accessible. In the UK, accessing drugs can involve making a case for exceptional or compassionate use, or joining a trial. It can also involve challenges to NHS trusts, NICE decision making and efforts to raise funds privately. For advanced or metastatic patients in particular, targeted drugs which offer extra months of life with symptoms held at bay are highly valued. However, for health systems, methodologies that determine efficacy based on a range of factors including quality of life, balancing wider public benefits through effective allocation of healthcare resources, mean that these benefits are not always sufficient to warrant approval. This has led to a series of disputes around access to tailored therapies, for example Avastin (for ovarian and colorectal cancer) and Kadcyla (for breast cancer) in the UK, with some patients turning to charitable fundraising or private funds to access these and other drugs. These campaigns can have a considerable media profile, giving a sense that these activities are both common and necessary, intensifying a media discourse of the NHS as failing to provide. This has enrolled patients in campaigning for access alongside others affected, as well as relatives and other advocates, something we discuss in Chapter 6. For example, with regard to a recent campaign for access to Avastin by a cervical cancer patient who had been denied treatments available in England but not in Wales, ITV news quoted the patient: ‘I feel very angry about it, it's so unfair – this is playing with people's lives. But I'm fighting it for others both in England and Wales, and for those who are too afraid to speak out.’ 5 Patients seeking access to these kinds of treatments also have to navigate personal networks and complex healthcare provision, including sometimes predatory markets, as Keir, a campaigner for better drug access for cancer and other patients, described:
there are certain circumstances where … crowdfunding [is for] a medically reputable drug … But it's horrendous that patients are being forced to take that, it's a hugely stressful undertaking for them. They're trying to do crowdfunding, they've got neighbours who are … running charity events … they've got to … give a huge amount of themselves to try and thank everybody, and engage everybody to try and get enough money in the door, on top … managing cancer treatment … trying to do their day job, and continue to bring up their kids … that is a real … system failure.
Uncertainties, doubts and disappointments have also proliferated alongside these drug developments and campaigns for access. As practitioners in our research often attested, cancer is complex and ever-changing, and drugs rarely deliver the kinds of benefits seen with the paradigmatic cases of Herceptin or Gleevec, as this oncologist describes:
No, no targeted therapy has yet made otherwise incurable metastatic cancer curable. What they have done has meant that in the same way that chemotherapy can prolong survival from six months to two or three years in breast cancer or bowel cancer, there are now diseases like melanoma and renal cancer where previously chemotherapy didn't have a role where now patients can live two, three, four, sometimes longer. But they are only seeing results akin to what we see in breast cancer with hormone therapy or with Herceptin.
So … they haven't been the, the sort of paradigm shift … which we had hoped they would be … fifteen years ago … the way these drugs were sold was that they were going to take cancer and turn it into a chronic disease, like hypertension or like diabetes … [this] a huge new era hasn't materialised. What instead we're seeing is a new generation of drugs, sometimes but not always … less toxic than chemotherapy that, that add to the armamentarium of treatment that we have, but haven't had that effect of, of, of meaning that people live ten, fifteen, twenty years, whereas previously they, they would only have lived a few weeks or months. They now live for many months or a few years, rather than several months or a year.
And do you think patients understand this?
I think patients’ expectations of … cancer treatments generally are … are over-optimistic.
These concerns are echoed across professional and social scientific literatures. Social scientists such as Davis (2015) have argued that patients’ overestimation of the benefits and underestimation of the toxicity of these treatments is a systemic problem rather than a feature of individual patient-clinician decisions. For Davis, permissive regulatory environments, government promotion of bioscience markets as a vehicle for economic growth and national competitiveness, and close ties and connections between industry, oncology, government and patient organisations have fuelled a culture of overtreatment, as have scientific and media reporting and medical practice intent on maintaining hope in the fight against cancer. As Davis notes, ‘Publication bias, distorted scientific reporting, promotional material, and stories of “miracle” drugs percolate against a background discourse of “science at a crossroads” and “new eras”’ (2015: 213).
We must nevertheless recognise that patients are not simply dupes of this promissory bioeconomy. Instead they are active participants in its articulation and contestation. Patients in our study were by no means predominantly pessimistic nor wildly optimistic but, instead, were often strategic and nuanced in their engagement with these new therapies. Even patients funding treatments privately had a careful analysis of why they were taking this approach. Phil, a patient with advanced bowel cancer who was self-funding Avastin, explained:
look, you know, I'm in a situation where I've got advanced bowel cancer … I can afford to do it, fortunately, so I thought … although it's expensive … I'm going to … give it a whirl. … I don't want to … die wondering whether … it would've made a difference or not.
Others told us how they had accepted not being able to access targeted therapies. Alison, a patient advocate in her mid-sixties who had previously worked in special education, who had experienced pancreatic and breast cancer, described her philosophy thus:
Now my brother works for [a pharmaceutical company], he used to work for them in America. He says ‘we've got a new drug’ but we spoke to the surgeons here, I couldn't do it because … it hadn't been passed [by the regulator] so nobody could administer this drug, they had great success. [My brother] got all my test results, he said ‘right, you have a very rare type of pancreatic cancer … and this drug seems to be working’. So he speaks to the oncologist [who says], ‘No you can't do it because it's not licenced.’
So I went ‘that's fine’ … things happen in life for reasons, ok … it's part of our journey … it wasn't for me … It's like … if you're buying a house or something and you miss out on it, it wasn't meant for you, don't worry or stress about it … What's meant for you, will happen and it might be even better.
Alison told us how her family rallied around her when she experienced her first cancer. Her daughter, a veterinary nurse specialising in cancer, made time to pick her up after her appointments, while her husband sought out second opinions and support networks. Drawing on their social and cultural capital, cancer patients and their families navigate the stage and subtype of their cancer and access to treatments that might extend their future. This not only involves building from and troubling cancer identities of survivorship and developing novel campaigning tactics and alliances, but it incorporates more ordinary ways of living with uncertainty and hope. Through these kinds of activities and other reflections, patients, relatives and practitioners come to terms with the opportunities and setbacks of personalised genomic medicine for cancer, even as they might also articulate other, much more overt promissory discourses elsewhere. These themes cut across the chapters to follow and are explored in particular depth in Chapter 6.
Personalising prognosis, prediction and diagnosis
Effectively targeting treatments relies on molecular markers; together they are reconfiguring how cancers are classified (Nair et al. 2018). New molecular markers, disease categories and targeted treatment options are part of a nexus rather than a linear process of discovery and intervention. This means that prognostics, prediction and diagnosis, always rather dynamic in the context of cancer, are becoming even more so, as genomic tests and assays provide ever more data on a patient's risks, mutating tumour and responses to treatment. Diagnosis and therapy ‘bleed into each other’ as Bourret et al. (2011) note, transforming clinical decision making as the results of genomic testing rework established understandings and practices.
In addition to molecular subtypes of blood and breast cancers, as discussed above, there are now a range of established molecular markers of other cancers such as colon, lung cancer, ovarian and melanoma. For example, colorectal cancers can be classified according to five biomarkers including KRAS. Particular mutations can also be found in different kinds of cancers; for example, the KRAS mutation has been identified in colon and lung cancers, and the BRAF mutation has been found in colon cancer and melanoma. As treatments are increasingly guided by molecular profiling, not just the location of cancer in particular areas of the body, professionals have begun to discuss a new paradigm of diagnosis and classification based on such molecular markers, as in the excerpt below:
It is the mutation-guided therapeutics, rather than the traditional cancer type-dependence classification, such as that based on classical anatomy and histology, that has etched a new context … This concept has compelled a paradigm shift. Now patients with BRAF V600E mutations would be prescribed the same drug regimen irrespective of their cancer type and location, for example, acute myeloid leukemia, breast cancer, or melanoma. (Nussinov et al. 2019)
Cancer has traditionally been diagnosed histologically, through the microscope. Serum markers such as the prostate antigen test (PSA) were subsequently developed for monitoring those with or at risk of cancer. This focus on biomarkers was also brought together with advances in the understanding of oncogenes and tumour-suppressor genes and genomic technologies to develop a range of biomarker companion tests for proteins associated with specific subtypes of cancer, such as HER2. The successes of Gleevec and Herceptin were promising, but in fact the complexities of cancer are such that there is rarely only one gene of central importance in its development, and testing moved towards looking at groups or clusters of molecular biomarkers that would assist with defining and, crucially, predicting the course of the disease or the usefulness of one particular drug, not least to avoid ineffective treatment. Gene-expression profiling has developed to identify patterns within cancer tumours and this has led to the identification of subtypes based on these patterns for cancers such as leukemia and breast cancer. This has developed into a range of tests to aid treatment decision making, particularly for breast cancer, many of which are commercially available and based on proprietary algorithms. MammaPrint® (Agendia, Amsterdam) was one of the early multi-gene panel tests to be approved by the FDA in 2007 to predict breast cancer relapse. Oncotype DX® (Genomic Health, Redwood City, CA) is also used to predict the risk of recurrence of certain kinds of breast cancer in order to aid treatment decisions, as we go on to discuss in Chapter 2. Cambrosio et al. have written about how these tests were developed by scientific and commercial partners in concert with evolving regulatory arrangements, ‘forming heterogeneous assemblages that seek to singularize treatments’ (Cambrosio et al. 2019: 2).
Novel molecular tests are particularly interesting because they involve rearrangements of private–public relations, pathology and clinical decision making around prognosis and prediction (Kohli-Laven et al. 2011). For example, MammaPrint and Oncotype DX were developed in company laboratories to which clinicians must send samples for analysis. Results are returned in the form of reports of likelihood or risk of recurrence to form part of a broader set of results from other non-molecular tests and other information that clinicians use as part of clinical decision making. The roles of hospital-based and regional pathology services are also reconfigured through the development of oncogene sequencing, both in-house and externally, resulting in tensions and threats to professional autonomy that have to be managed. This includes pre-screening to identify low-risk cases where proprietary testing might not be cost-effective (Dabbs et al. 2018; Beaudevin et al. 2019). As Nelson et al. have argued, these genomic tests, together with the therapeutic regimes they invoke, are part of a new paradigm of ‘actionability’ in cancer which is transforming alongside trial arrangements, regulatory processes and healthcare, where the ‘articulation of molecular hypotheses and experimental therapeutics become central to patient care’ (Nelson et al. 2013: 413). They note, however, that this brings uncertainty about how to make meanings from molecular results: actionability is thus an ‘experimental space’ where different approaches and interpretations coexist and must be resolved in the ‘knowledge architecture of clinical oncology’ (Nelson et al. 2013: 413).
Within this space, clinicians and patients must also engage with molecular results about cancer as another layer of information that has to be analysed, interpreted and considered in relation to other aspects of the patient's disease, including lifestyle, emotional state and social location, and their capacity and appetite for further treatment. Making a genomic test valuable as part of their decision making includes making sense of intermediate or ‘grey areas’ and crafting reassurance or managing the anxieties that ensue. Patient experiences of tests using biomarkers (not genomic technologies) highlight some of the intricacies of these processes. Bell and Kazanjian's (2011) research on PSA, a molecular marker which is used to monitor the risk of prostate cancer developing, progressing or returning, shows how the responsibility to be well is managed by patients and practitioners through engagement with these results. Although its effectiveness as a screening or monitoring tool is highly contested because of questions about its predictive value (Bickers and Aukim-Hastie 2009), its continued use in some contexts can be explained by neoliberal governance whereby individuals become responsible for identifying and minimising their risk of disease (Petersen and Lupton 1997). Bell and Kazanjian (2011) show how men experiencing the test had to navigate considerable anxiety and uncertainty, together with expectations of action from family members and clinicians as part of the process of being responsible. They argue that molecular measures intensify a sense of living with cancer even when results suggest lower risks, echoing the findings of Hamilton's (1999) study of women's experiences of CA-125 biomarker monitoring for recurrent ovarian cancer, another contested measure that lacks sensitivity and specificity. Quoting from Hamilton, Bell and Kazanjian note:
Many women begin to identify their CA125 levels of the evidence of disease status. If it is low, they feel relieved and in control … If the level is elevated from prior levels, they know the disease is back and must plan for more treatment. Unfortunately, even normal insignificant fluctuations in CA125 levels take on enormous meaning. As a result, emotional well-being may come to depend on lower CA125 number, even if numbers remain in the normal range. Patients may find themselves on an ‘emotional roller coaster’ with ups and downs determined by the direction of serum blood levels. (Bell and Kazanjian 2011: 193)
In later work, Bell goes on to note that this sense of what Gillespie (2012) has called ‘measured vulnerability’ can be intensified by molecular biomarkers, whereas for other patients these results do provide reassurance because of ‘the semiotic potency of biomarker numbers as transparent, material indices’ (Bell 2013: 230) in the context of ongoing uncertainty and fear around cancer.
Results such as these nevertheless create a space for patients to negotiate the meaning of their illness and treatment arrangements with their clinicians, ‘empowering patients to challenge physician decision making – especially in circumstances where physicians are seen to be overly passive or nihilistic’ (Bell 2013: 139). Genomic results add a further layer of complexity to these processes, promising more precise personalisation but also requiring work to make sense of results in a responsible manner. Our analysis of personal blogs and online forums discussing Prolaris (Yan 2017), a gene-expression profiling test to support therapeutic decision making for prostate cancer by predicting a tumour's potential aggressiveness, suggests that the responsibility to be positive is powerful. Men crafted ‘peace of mind’ through their engagement with the test, even when the results were negative or unwelcome indicators of foreshortened futures. These positive registers of responsible patienthood were reinforced in company blogs and through virtual patient networks which together advocated for genomic testing as a means of patient support.
As molecular profiling to determine treatments matures and expands through the use of genomic technologies, many more patients with or at risk of cancer developing or returning will be drawn into this kind of work, managing uncertainty and the anxieties it can provoke, finding reassurance and making meaning out of test results with clinicians and/or other affected individuals they encounter in face-to-face and online support groups. Here they are crafting identities and futures together, seeking to realise value from tests in the process. Patients actively seeking access to tests might also be drawn into regulatory decision making, just as with targeted treatments, perhaps working with industry, charities and/or clinicians and scientists as these experimental spaces become more mainstream. This involves crafting bigger futures and engaging in valuation work for industry and government, whereas for other patients who are less engaged, active or well, future-crafting takes place on a much more local scale. We go on to explore this further in Chapters 2 and 3 where we focus on two very different tests and scales of future-crafting, work and value making for breast and gynaecological cancers.
Since the development of Herceptin and Gleevec a whole host of molecular markers and targeted therapies for cancers have emerged. Among these are therapies which target the BRAF mutation in metastatic malignant melanoma (Vemurafenib), the EGFR mutation in non-small-cell lung cancer (Erlotinib and Gefitinib) and the KRAS mutation in colorectal cancer (Cetuximab). Similar to the stories of Herceptin and Gleevec, these therapies emerged through complex trial and organisational arrangements, including the involvement of public–private partnerships, international collaboration and patient groups. Participation in trials for other targeted therapies, or combinations of therapies, has become a more common expectation for cancer patients, as has access to experimental drugs (although trials and drugs are not accessible for all patients, as this depends on their health, prior treatment, type or stage of cancer as well as genomic-based eligibility). This involves patients and their advocates in a range of activities to understand, source and secure particular treatments or combinations of treatments through being on trial, as access to personalised therapies becomes an expected part of the patient journey, reinforced by the promise of personalised cancer medicine.
Cambrosio et al. (2018) stress the importance of understanding this ‘reshuffling’ of the research/care distinction and new forms of ‘experimental care’ that have emerged in personalised cancer medicine. This draws our attention to the care enacted and received by patients while on clinical trials which are increasingly adaptive or novel in other respects (for example, umbrella and basket trials which bring patients together based on their molecular profile, not their cancer types), as well as experiments in care that take place beyond involvement in trials through a culture of ‘trial and error’ approach to treatments. The world of targeted treatments is one of novel combinations, unknown side-effects, tumour heterogeneity, resistance, adaption and evolution. Patients, together with family members, clinicians and scientists, are researching together as they navigate the meanings and possibilities of molecular diagnostics and therapies. This is no longer simply testing and treating accordingly in a linear fashion, but treating and profiling in iteration, adapting treatments and, increasingly with the development of so-called liquid biopsies that test circulating tumour DNA (avoiding the need for invasive biopsies), retesting as a form of theranostics. Research is also becoming embedded in care through architectures such as the SHIVA 6 trial's Molecular Tumour Boards and other larger-scale infrastructure such as cohort management systems that have remained in place after the trials have ended as a means of integrating research and care more routinely through directing patients to trials and/or novel experimental treatments as part of their care:
The body of the patient becomes simultaneously a locus of experimentation and the subject of hopefully more effective (because more precisely tailored) care. To put it in a slightly different way, experimentation on an individual patient also qualifies as a form of personalized care. (Cambrosio et al. 2018: 218)
Together, these new practices are reconfiguring patients’ and professional and institutional futures. Hopeful futures of remission and even cure are cultivated alongside visions of more efficient services and responsive professionals. These promissory big futures are enacted in trials and experimental treatments. But other kinds of more provisional and, at times, unwelcome futures remain in play, as the complex realities of vulnerable bodies and institutional processes emerge and impinge on these processes.
As well as being built around a multi-drug regimen, these new trial arrangements rework assessment criteria to demonstrate therapeutic benefit. As Keating and Cambrosio (2011: 365) note, this involves new ‘end-points’ such as ‘disease stabilization, time to progression and progression-free survival’ for phase 2 and 3 trials, reworking goals for the future in the process. It is also worth noting here that although randomisation is common in other trials, this has always been controversial in cancer, and the genomic era has involved an acceleration of new trial designs which do not involve randomisation. Keating and Cambrosio (2011) note that a general feature of these kinds of trials is that they are not statistically robust, tending to involve small numbers of patients and a lack of ability to compare targeted therapies such as Herceptin with other combination therapies, thereby tending to bias findings in favour of Herceptin-based combinations. Adaptive trials are part of the experimental process, rather than a fixed methodology to be applied routinely, and the nature of supporting evidence is co-produced in a clinical context where the promise of the drug holds great sway.
The changing nature of trials and issues over access and efficacy have not only drawn more patients into experimental practices as part of their treatment, they have also sparked international debates around measures of success and clinical trial design, as well as the processes for approval based on clinical effectiveness in which trials play a crucial role. Trial design, pricing structures and measures of efficacy of tailored, precision or stratified cancer medicines are all areas of flux at the present time, generating public doubt about the promise of personalisation and its role in cancer care now and in the future. This has taken the form of controversy around the extent to which precision or personalised medicine is worthy of the celebration and expectations in popular and professional discourses about its possibilities. Borad and LoRusso list some of the problems with establishing benefit in this area as follows:
selection bias present in single-cohort studies lacking a control arm, ascription of success to alterations being identified simply as actionable (instead of more rigorous criteria that would classify alterations as useful or not on the basis of strength as a predictive marker for therapeutic efficacy), or leading to change in therapy (irrespective of such a change producing a favorable outcome), heterogeneity of histologic tumor types, and inflation of value of broad-based NGS profiling in the setting of inclusion of patients with well characterized alterations (e.g., patients with BRAF V600E melanoma) in reported studies. (2017: 1583)
As the authors go on to discuss, the SHIVA trial mentioned above is an oft-cited example of the difficulties with researching precision medicine. The first SHIVA trial did not find any benefit in therapies allocated on the basis of genomic profiling as compared to therapies allocated using conventional clinical decision-making tools. A second SHIVA trial is, however, ongoing and, despite the problems with the first trial, SHIVA has been hailed as a success in clinical trial design because it did suggest that targeted therapy based on profiling might be a valid approach in a subgroup of patients with a particular kind of molecular alteration. 7 The lack of definitive proof of benefit from (randomised) trials has been taken by some critics as evidence that personalised or precision medicine is over-hyped. One haematologist, Vinay Prasad, who has a significant social media profile, has taken issue with precision medicine trial design in particular, especially relating to the lack of randomisation and replicability. This, in turn, has prompted criticism from advocates of personalised medicine, who suggest that flexibility is the new (and ethical) approach to meet patient needs, eschewing the rigid orthodoxies of the past. 8 Here we see some of the disputes about the promise of personalised cancer medicine laid bare as the valuation practices of trials are openly contested in professional and public forums.
We can situate the emergence of these trials and debates about their efficacy as part of the wider bioeconomy of promissory capitalism, where disease-free futures are continually re-envisaged (Cooper 2008; Michael 2017b). Expectations about personal and collective futures feature prominently in these regimes (Good et al. 1990; Novas 2006; Haase et al. 2015) as ‘future-oriented discourses drive and shape innovation projects’ (Borup et al. 2006: 285). Yet as Brown and de Graaf (2013) demonstrate, both hope and despair are key to trial arrangements in practice (see also Cooper 2008; Will and Moreira 2010; Cooper and Waldby 2014). The cultivation of low expectations among patients has also been shown to be a way in which clinicians manage the hype of contemporary biomedicine (Gardner et al. 2015), something we return to in Chapter 4.
Brown and de Graaf (2015) analysed the lived experiences of advanced cancer patients involved in phase 2 and phase 3 randomised control trials. Their research found that hope can be a means of managing the uncertainties associated with prognosis and treatment success. However, when negative eventualities and limited time horizons are introduced, patients engaged in ‘bracketing off’ the future, to limit reflection on the difficult realities that might lie ahead. These descriptions challenge conceptions of time as ‘linear’, with reflections on cancer necessarily encompassing an orientation towards the future in the present.
Montgomery's study of adaptive trials suggests that moving away from standardised approaches to ‘predictable uncertainty’ is premised on ‘modes of knowledge production which claim to know the future’ (2017b: 232). As trials speed up to deliver treatments to patients sooner, Montgomery argues that probabilistic logics are replacing promissory logics on which standard randomised trial designs are based. Here, adaptive trials are oriented around negotiation of unknowns as part of ongoing experiments, creating moral value, not just commercial value, for a diversity of actors. Optimisation through adaptability and iteration becomes key here, maximising the best possible future for patients amid uncertainty. Montgomery notes that such benefit tends to be framed as collective rather than as one for individual patients. There is a need to explore the implications of these processes for patients as they go through these trials.
We know from other studies that what Lamprell et al. (2018) aptly call ‘the road of trials and obstacles’ places numerous demands on patients. In their study of cancer patients’ experiences of BRAF mutation testing, targeted treatments and associated trials, they discuss how BRAF mutation testing might be offered as part of efforts to secure access to a trial, but this is not a straightforward process. As in the case of one patient in their study, delays can mean that the trial closes before the tissue samples are analysed, and patients can find themselves having to transfer to another hospital to participate in the trial. Patients also have to manage a host of side-effects from experimental treatments accessed via trials, sometimes becoming too ill to continue. For others, accessing the drug via a trial can prove to be a lifeline, although not without ongoing complications to be lived with while in remission, with other drugs prescribed to manage side-effects. This points to the importance of patients’ hope, trust and vulnerability in crafting futures in cutting-edge cancer care, themes also in Brown et al.'s research on the imperative of hope and trust in clinical trials (Brown et al. 2015).
We find echoes of this across our research, captured in the extract below, taken from a joint interview with two breast cancer patients, Laura and Viv. Both had late-stage cancer diagnoses when they had young families and were now living with secondary breast cancers. They got to know each other through their secondary cancers, which put them ‘in a completely different place [to primary cancer patients]’, as Laura explained. During the interview, they talked about the work they had done to find out about trials and their advocacy around access to drugs. Viv received a standard treatment drug to which she responded well, whereas Laura, after receiving various chemotherapies, got on to a trial of a targeted therapy which she takes in tablet form alongside Herceptin. Laura told us she had secured the ‘last place’ on the trial, at a point when she had ‘failed on quite a few lines of chemotherapy so … was running out of options and … probably only had less than six months to live’. She continues:
[Laura] I remember we went away to [city overseas] as a family because I kind of thought ‘this might be my last big holiday’. And my consultant … when I came back I thought I'd be going on possibly my last line of chemotherapy but when I got back he'd contacted his friend in [another city] and he said ‘there's a slot on this trial’.
[Laura] … there's an international trials database and I'd been sending … my consultant, links to … I remember trials in France and Belgium. And I think most of them were immunotherapy trials – I didn't know that – but he said to me ‘oh, I'm not sure about these, it's still pretty untested in breast cancer, the response rate is very low. I really don't advise … you'd have to go and live in Belgium or France or wherever for a number of months, is that feasible?’ So he wasn't keen. But to be fair to him, he obviously did contact the [cancer centre in another city] and there was one place left on this trial and I thought ‘I've got nothing, absolutely nothing to lose.’ But no, he knew nothing about my, you know, molecular profile at all. But within a fortnight my cough had gone, I felt I was, you know…
[Viv] It was quite miraculous, actually.
[Laura] It was, it was a really strong, very strong response. And after three cycles of the drug, I got scanned and the cancer in my lungs had been, you know, just obliterated and it stayed like that.
[Viv] The thing is, when you're dealing with that sort of possibility of a trial with the drugs that are coming through, you just think, you know, it should be advertised.
[Laura] It should be.
[Viv] It really should be.
[Laura] And it's just been pure chance, luck.
[Viv] You can understand why we do what we do because you just think you're given this second chance at life really, aren't you, by a drug and you just think ‘OK, I might have two years or three years but I'm going to make that two years or three years matter within the whole scheme of breast cancer for women really.’
[Laura] What's frustrating for me though is the drug has been really successful. So … I know there were 11 of us on the trial. There's me and one other lady still on it after two years – I think sadly the other women have died. But I saw a poster presentation from the company and they said it's had a 67% response rate in this very early phase one trial.
[Viv] Which is amazing.
[Laura] Which for women who've been heavily pre-treated, it's a really good response rate.
[Laura] And they described it as being ‘unprecedented’ but for some reason they've not taken it forward to phase two. So when I tell my story at different places, I always have people coming up to me, saying ‘what drug are you on, what trial is this?’ And I have to say ‘I'm really sorry but I'm kind of on it, I got the last place and they don't seem to be … at some point they'll take it forward but they don't seem in any…’
[Viv] … rush, yes. Right, let's just say ‘you've got to do it, you've just got to do it!’
As this exchange suggests, participation can extend from negotiating individual access, in concert with clinicians, to include more concerted collective efforts to open up more trials and more access to trials for other patients. It also includes managing hopes and expectations for oneself and others as the research progresses, and when personal benefits and findings do or do not materialise. Patients can take an active role in challenging clinicians, not just in relation to their own treatments but trial design too. This has included challenges to the exclusion criteria for clinical trials, as in the example of a US physician, Dr Kelly Shannon, who has metastatic breast cancer and has campaigned with patient organisations METAvivor (established in 2009 to provide funds for research) 9 and METUP (formed in 2015 and drawing inspiration from the AIDS activists ACTUP) 10 to open up access to trials to patients who are not just what she describes as the ‘healthiest of the dying’. 11 Patient representatives are also increasingly involved in trial-management processes via patient and public involvement advisory groups and panels. This is now a routinised feature of cancer research. But acting as a representative in complex adaptive trials and other kinds of studies such as whole genome sequencing initiatives, as discussed below, can involve detailed engagement with the complexities of genomic science as well as trial methodologies, project governance, engagement and ethics.
Yet as Llewellyn et al. argue, based on their research on patients with brain cancer, trials take place in the context of ‘the contingent and improvised nature of care’, where doubts and uncertainties can be overshadowed by ‘an unduly optimistic and “can-do” attitude to management based around a technological imperative and medicine's mandate to extend lives’ (Llewellyn et al. 2018: 413; see also Kaufman 2015). Focusing instead on the ‘unsettling and wavering terrains of disease and care’, they explore how patients navigate experimental treatments, necessitating detailed engagement with research, medical travel and NHS bureaucracy (Llewellyn et al. 2018: 411). This includes managing being excluded from participation in trials to access new therapies such as Avastin, a targeted chemotherapy (not available to one patient in their study due to his prior involvement in an immunotherapy trial abroad), as well as crowdfunding efforts to access drugs considered by the NHS to be of unproven benefit. These kinds of ‘unimaginable dilemmas and hard-to-swallow paradoxes’ are part of the terrain of targeted treatments for cancer (Llewellyn et al. 2018: 420).
It is also important to appreciate that patients who actively seek out trials do this from a range of backgrounds and perspectives, not always based on detailed engagement and knowledge. One oncologist gives an example of this:
I've had a GP … being treated in another institution … phone because they've read on the internet about a clinical trial that was taking place that they've seen the inclusion criteria for that they want to be included in. [But this goes] all the way through to people having absolutely no idea, you know, really what a clinical trial is, a clinical trial is being a guinea pig … I've – somebody said it to me this week in fact … bizarrely this person said it to me … he said, ‘Oh, I just want you to know … that I'm quite happy to be a guinea pig.’
Adaptive trials of targeted treatments can make cancer patients partners in experimental healthcare, but the extent and type of their engagement in the processes of the trial, including its design, purpose and outcomes, varies considerably, as do their experiences of access and care. Trials might be based on optimising the future for patients as a whole, but individual patients are also heavily invested in extending their own future. Trials are complex, just like cancers and patients, which brings considerable negotiation and articulation work for patients and their practitioners, not just to enable access but to keep hope alive for patients in and around the trial, as we discuss further in Chapter 4.
Whole genome sequencing
Developments in large-scale genomic sequencing are another feature of clinical oncology and associated research. More genetic information is being collected about more kinds of cancers, often through research studies. Whole genome sequencing (WGS), in which the entire genome is sequenced rather than panels (or groups) of genes – an approach associated with molecular diagnostic tests (often proprietary) and targeted treatments – is an important aspect of these developments. As Nakagawa and Fujita comment,
Whole genome sequencing (WGS) approaches can be used to comprehensively explore all types of genomic alterations in cancer and help us to better understand the whole landscape of driver mutations and mutational signatures in cancer genomes and elucidate the functional or clinical implications of these unexplored genomic regions and mutational signatures. (2018: 513)
WGS has a profoundly exploratory logic, charting previously unknown territories of the genome to reveal its complexity (Martin 2018). As Brown and Michael (2003) note, innovative technologies often build upon past ‘failures’ while ignoring the possibility of their own failure. This pattern appears to be being replicated in the case of WGS: its role in transforming cancer care is being assured through major infrastructure developments in the NHS, and the lack of ensuing ‘actionable results’ is not being framed as problematic.
At this point, genomics meets biobanking, often incorporating other clinical datasets where patients have given consent for their data to be reused. Digital processes of analysis are crucial to handling these vast quantities of data, as are private–public partnerships to deliver the technology and interpretative power required. The creation of value from these datasets requires both the centralisation of data and its ultimate detachment from the state (Cool 2016), in a process through which populations become brands with bioeconomic potential (Tupasela 2017). The promise of a growing bioeconomy aligns with a vision of health services that deliver better care to more patients via ‘benefit sharing’ (Hayden 2007), for example, where companies offer medical innovations to the health service that provide the data at a preferential rate. Yet these benefits remain opaque and promissory, sometimes bewildering to patients and participants already caught up in ‘surveillance capitalism’ where rights to privacy are routinely signed away as part of ordinary consumption (Zuboff 2019), and where publicly funded health systems are struggling to pay for expensive medicines such as targeted cancer therapies. How the ‘regularized, embodied work that members of the national population are expected to perform in their role as biobank participants’ (Mitchell and Waldby 2010: 334) is to be recognised or rewarded in such contexts is radically unclear. The ethical complexities of this are compounded in cancer, where benefits may not be felt, futures compromised and legacies uncertain.
Tarkkala et al. explore some of these dynamics in their research on personalised medicine in Finland – ‘an intensely state-driven and national endeavour’ (2019: 143) – analysing detailed policy plans and institutional strategies for embedding personalised medicine in Finnish healthcare. This work spans ‘business, from financing to marketing, resource and personnel management, scientific research, product development, consulting, and public governance and policymaking … experimenting with existing epistemic, professional, institutional, political, legal, administrative, and business orders’ (Tarkkala et al. 2019: 143–4). Wealth creation is a central theme of these efforts, realised via intensified innovation, commercialisation and data-driven medicine, which they note builds on two decades of promise that can be traced to the development of deCode Genetics Ltd in Iceland (Fortun 2008; see also Rajan 2006).
The discourses that surround these ventures are highly promissory, focused on delivering benefits to the nation, as well as patients and individual participants, but often hedging the later possibilities against the complexities and risks of the processes and the need for new infrastructures to be developed. Institutions are constructed as slow or even resistant to change and the success of WGS is predicated on transforming laboratory services and professional cultures, echoing the democratising ethic of corporate actors such as 23andme (Prainsack 2017). As well as recruiting patients as active collaborators in its genesis and implementation, health systems too need to be made ready for personalised medicine as expressed in policy documents such as the following:
Predicting which patients will benefit ahead of time, using information from an individual's cancer genome to improve overall outcomes and minimise toxicity and cost, is the clear path forward. To achieve these goals, health systems need to evolve from their current state, to a more personalised model of cancer care with targeted therapies, driven by more precise and genome-driven research and diagnostics. This is a central tenet of Precision Medicine. (Scottish Scientific Advisory Council 2019: 5)
Just as new institutional requirements to better manage interpretation and clinical decision making based on results emerge from these innovative, commercially oriented, data-intensive initiatives, so too do new arrangements for the professional training and ethics required to support data generation, curation and exploitation. Consent to participate in research and the management of so-called ‘incidental’ findings supplementary to a patient's cancer (typically in relation to genetic risk for inherited disease) are a particular focus of attention here, given the importance of widespread participation to the success of these ventures (Dheensa et al. 2018). But these are complex endeavours, marked by numerous misalignments between policy, strategy and practice, given the complexities and pressures of healthcare systems. In the UK, and the NHS in England within it, the 100,000 Genomes Project is an exemplar of the kinds of large national initiatives that are delivering WGS, which we discuss further in Chapter 5.
The promise of personalised or precision medicine for cancer is contested in medicine, science and beyond in the public sphere because of concerns about efficacy and cost in particular. As Interlandi (2016) argues, ‘early attempts to tailor disease treatment to individuals based on their DNA have met with equivocal success, raising concerns about a push to scale up such efforts’. Tim Maughan, from the CRUK/MRC Oxford Institute for Radiation Oncology, notes that personalised medicine for cancer has thus far proven to be of limited clinical benefit, quoting a study which found that ‘overall survival from 71 targeted cancer therapies approved by the FDA between 2002 and 2014 was only 2.1 months’ (Fojo et al. 2014). He continues:
The consequences of heterogeneity, clonal evolution and the influence of the host response are that simple genetic tests are much less accurate in predicting prognosis and treatment response than was expected based on the CML imatinib paradigm. Similarly, targeted drug therapies may show an initial response, but this is rapidly overtaken by tumour regrowth due to emergence of tumour clones often demonstrating multiple different mechanisms of resistance. Despite this, personalised cancer medicine, now enhanced by immunotherapy, is still projected as the existing paradigm, and supported by major cancer centres across the world, by pharmaceutical and diagnostic companies alike. Researchers in the field and especially pharmaceutical companies are acutely aware of the challenges, but still clinicians, patients and their advocates pursue access to these targeted agents with enthusiasm. (Maughan 2017: 15) [our emphasis]
Maughan captures the key dynamic of anticipation and concern that we find across the various developments in genomic medicine for cancer reviewed in this chapter and explored further in the chapters that follow. Personalised cancer medicine is replete with promissory claims and instances of optimism and hope. Yet these tropes and possibilities are fragile and contested, when they emerge in everyday encounters, collective action and in the more stylised pronouncements in policy and the media.
What we stress here, however, is that these activities need to be understood as part of, rather than auxiliary to, the innovative and experimental processes in personalised medicine for cancer. Innovation and experimentation extend outwards from the dataset or the laboratory, the scientist or the entrepreneur, to the clinic and beyond, to the regulatory and public sphere, and in networks and relations with fellow cancer patients, families and friends. Across these settings, practitioners, patients and their families are doing emotional and articulation work (Star 1985) as they co-produce the meanings of novel genomic treatments, tests, research and relations, crafting their and others’ futures as part of this process. Anticipation and moderation are part of navigating individual and collective futures and creating various kinds of value, from the big futures of bioeconomic growth for the nation to individual, more personal futures of feeling cared for and valued. Just as molecular diagnosis, targeted therapy and subtypes of cancer and cancer research and care are entwined, interactive and co-produced, so too are individual and collective futures. These experimental relations, processes and categories enrol increasing numbers of patients and practitioners not just in research or data collection but in new kinds of regulatory and funding arrangements, patient collectives and public engagement activities.
In what follows, we endeavour to explore these interactions and interweavings to give a detailed account of the kinds of value that various sorts of work create as genomics personalises cancer medicine. We explore the activities and narratives of patients, practitioners and family members that make genomic medicine valuable in policy and in practice but can be hidden or unacknowledged. Looking at the kinds of futures being crafted and how experimental and articulation work in personalised medicine for cancer is distributed and enacted across these settings, we go on to consider what happens when we begin to value it as a contribution to innovation, and how this might change how we share the benefits and risks of personalised cancer medicine now and in the future.