In Vivo: strategic insights for life sciences decision-maker...
By Lucie Ellis 24 Feb 2020
The biopharma sector is often accused of a being a slow-moving engine, but a look back over the last 20...
Survival is a statistic that has gradually come to dominate the public narrative around cancer, marking the hoped for transition of the disease from a death sentence to a treatable chronic condition. Since 1990, the number of US cancer victims still alive five years after initial diagnosis has increased by 20%, to a total of just under 16 million: the National Institutes of Health’s National Cancer Institute (NCI) projects survivorship will rise to more than 20 million by 2026. It’s a constituency of consequence, with the potential to re-shape cancer research and clinical practice toward a much more integrated, long-term perspective on the patient journey, from diagnosis to points beyond.
For biopharma, life after cancer is no longer a demographic blip, but a strategic business issue, with opportunities as well as obligations – particularly now that the cancer community is coping with a multiplying number of promising but powerfully complex immunotherapy drugs, whose late treatment effects on patients remain largely unknown. Exposure to these novel therapies is occurring against a backdrop of projected shortages of oncologists and especially primary care physicians, who are often the main providers of care for cancer survivors.”
All cancers are unique, so what has not changed is the association of survival with tumor expression. Whereas cancers of the lung, liver, brain and pancreas have stubbornly high mortality rates, some, more common malignancies approximate the status of a chronic disease. These include breast cancer, where the overall five-year survival rate following current treatment protocols is 90%; prostate cancer, at 98% for the vast majority of cases diagnosed early; cancer of the thyroid, also at 98 %; and many pediatric cancers affecting children under age 14, such as Hodgkin lymphoma and leukemia, at 98% and 86%, respectively. New drugs have figured significantly in accelerating this transition, with chronic myeloid leukemia (CML) a case in point: introduction in 2001 of the first tyrosine-kinase inhibitor,Gleevec(imatinib), helped raise the five-year survival rate in CML from only 31% in 1990 to 70 % today.
As the cancer life span lengthens, interest has moved from the invasive, one-off tools of surgery, chemicals and radiation to additional interventions geared toward minimizing toxicity and raising the quality of life for patients. A visible survivorship demographic has led to the embrace of a more holistic “treat the whole person” perspective centered on outcomes and surveillance, one involving a larger circle of providers, many outside the oncology space, to tackle numerous unanticipated effects of standardized cancer treatments. These impacts are surprisingly diverse, ranging from cancer recurrence, new cancers, and related disease co-morbidities to the lifestyle, psychosocial, and economic factors that affect patients’ well-being and long-term health status.
Overall, the statistics show that for many cancer patients there is a life after treatment measurable not in months, but in years (see Exhibit 1).In fact, according to the NCI, fully half of all cancer survivors remain alive 10 years or more post-diagnosis; many are victims of pediatric cancers who can now expect a normal life span. That’s clearly a positive – but it’s also a challenge. Dr. Mark Goldberg, a practicing cancer hematologist and regional board member for the American Cancer Society (ACS), tellsIn Vivo“What medical professionals are still struggling with is making survivorship an embedded institutional element of clinical practice, not just in cancer but also incorporating the front-lines of primary care.” A stark example of this disconnect is the continuing absence of a set of reimbursement billing codes categorized specifically for survivorship care.
Top 20 Most Prevalent Cancers In The USSource: CA: A Cancer Journal for Clinicians; August 2016
A 2016 report by the NCI concluded that the majority of older adults diagnosed with cancer present with two or more existing co-morbidities that are often exacerbated by the after-effects of standard cancer treatment.“Cancer can mask the impact of many chronic, pre-existing health problems,” says Lesley Solomon, SVP and chief innovation officer at Dana-Farber Cancer Institute. She notes that Dana-Farber is addressing this trend by having oncology sub-specialties in key areas such as cardiology, gastroenterology and endocrinology work in tandem with resident oncologists around care plans that address the entirety of an individual patient’s health profile and symptoms.“Integrated care is central to our approach to treating cancer, a perspective we see accentuated by the experience of our patients once they enter the post-treatment phase and begin their recovery.”
Survivorship as a distinct stage in the cancer continuum was formalized and endorsed more than a decade ago, in a 2005 report written by the Institute of Medicine (IOM, renamed in 2016 as the Health and Medicines Division) at theNational Academies of Sciences, Engineering and Medicine.Lost in Transition:FromCancer Patient to Cancer Survivorestablished four principles of survivorship care, which the report defines broadly as covering all cancer patients who have experienced the passage from diagnosis to treatment, recovery and beyond.There are four components of this care:(1) support for prevention and detection of new cancers and recurrent cancers; (2) surveillance for recurrence of new primary tumors, but with different clinical or biologic characteristics; (3) interventions for long-term or late effects attributable to cancer treatment or therapies; and (4) addressing the larger preventive health and psychosocial needs of cancer survivors through coordination between oncology specialists and primary care providers responsible for managing other chronic conditions with a bearing on a survivor’s overall health and well-being.
The public attention scored by the IOM report helped galvanize actions to operationalize these principles among a diversity of stakeholders, especially at the clinical stage. In the last decade, there has been agreement among all major professional, provider and patient groups active in oncology to single out and address the unique medical challenges confronting cancer survivors.“The survivor statistics may be emblematic of the success of science, but it also revealed that the difficult psychosocial adjustments as well as long-term and late effects of treatment were simply being seen by patients as the new normal – and that emphatically didn’t need to be the case,” said ACS SVP for patient and caregiver support Katherine Sharpe, in an interview withIn Vivo.
With support from the NCI and the federalCenters for Disease Control & Prevention(CDC), the ACS, as the oldest and largest voluntary health organization in the cancer space, launched a five-year plan in 2011 to build a consensus-based policy and practice platform on survivorship issues along with a repository of standards, evidence and information designed to put this issue out front as an advocacy priority for the cancer community. It has done this in the context of an unprecedented commitment to partnership with other cancer constituencies, from providers to patients, to researchers and regulators – and now, increasingly, to payers and big pharma as well.
The centerpiece of the plan is enactment of Cancer Survivorship Care Guidelines for use by clinicians and patient groups. With extensive input and evidence derived from a wide range of practitioners, four have been drafted to date: prostate cancer (2014); colorectal cancer (2015); breast cancer, jointly with the American Society of Clinical Oncology (ASCO - 2015); and head and neck cancer (2016). These guidelines form the basis for a templateSurvivorship Care Plan(SCP) to direct care designed for use by physicians in consultation with the patient.“The goal of the guidelines is to fill a gap in the cancer care system, whose prior focus was on diagnosis and the front-end treatment cycle administered by the oncologist.Instead, the Guidelines are oriented to assist the primary care physician on follow-up actions around active surveillance against recurrence and those ancillary interventions necessary to restore the cancer survivor’s overall health and wellbeing,” said Sharpe. “It’s the end user we see as most important, because defeating cancer for good is abetted by health-promoting behaviors like diet, exercise and tobacco/alcohol avoidance, as well as screening for both cancer late effects and chronic disease co-morbidities.”
Most leading cancer treatment centers, including Dana-Farber, now employ the SCP as a standard protocol in directing patient care, post-treatment. In addition to the ACS, ASCO, and NCI, theNational Coalition for Cancer Survivorship(NCCS) and theNational Comprehensive Cancer Network(NCCN) have endorsed or adapted the guidelines and the SCP template for use in clinical practice.
There is also a firm consensus on the priority health conditions that must be addressed in the context of an SCP consultation with the patient. The NCCN, which is the clinician’s main body for setting standard treatment procedures for individual cancers, has identified eight such conditions: anxiety and depression, including PTSD; cognitive/functional impairment; exercise, diet and other forms of preventive care; fatigue; pain; immunization and infections; fertility and sexual function; and sleep disorder.Recent additions to this list include lymphedema, or joint swelling; and anthracycline cardio toxicity, a late effect of certain widely used chemotherapy agents. NCCN’s work has been supplemented by detailed identification of more than a dozen cancer treatment side-effects produced by the National Coalition for Cancer Survivorship (NCCS), a patient advocacy group that is supported by all the big pharma majors and that recently fought to raise awareness of how efforts to limit access to opioids are lowering quality of life for cancer survivors with chronic residual pain.
The ACS currently has no plan to develop additional guidelines on specific cancers due to the challenges in finding the evidence base to drive their content.There is interest in a Guideline on lung cancer due to the increasing number of survivors in recent years, and efforts are now underway to remedy the information gap in this space, so work can go forward.
That conclusion reinforces a larger trend: as a still nascent field, survivorship lacks the evidentiary base that in medicine determines the allocation of resources. Slowly, however, survivorship is laying claim to a small but growing proportion of research dollars.Roughly 5% of the annual $5 billion budget of the NCI is devoted to grants and studies covering prevention, screening, quality controls, and other activities important to cancer survivors. The NCI also funds an Office of CancerSurvivorship to coordinate research on this issue through its contacts with other federal and state government agencies, academic medical centers, professional practice associations and patient advocates.
The most prominent recipient of survivorship research resources is pediatric cancers, which benefit from the significant progress in cure rates over the last three decades and thus the increasing ranks of recovering patients progressing into adulthood. The NCI survivorship office coordinates one of the federal government’s largest ongoing disease research programs, the multi-agency Childhood CancerSurvivorship Study (CCSS), which tracks long-term health status among 24,000 enrolled survivors of pediatric cancers from 1970 to 2000. This rich trove of data is an open resource for cancer investigators.
One ongoing project is whole-exome sequencing of 5,700 pediatric cancer survivors to identify genetic markers of vulnerability to secondary cancers, with other late effect studies to follow. Given the size of the survey cohort, CCSS is exploring use of mobile health technologies to better trace health outcomes over time. In a joint project with theUniversity of California San Francisco, NCI investigators are testing various in-home monitoring devices in patients to assess the relationship between cancer and the prevalence of cardiovascular-related conditions later in life. Researchers hope the work will produce a risk prediction model for cancer and heart disease that can help direct clinician’s attention to those most vulnerable.
Pediatric cancer survivor research got another boost with congressional passage in May of the Childhood Cancer, Survivorship, Treatment, Access and Research (STAR) Act (PL-115-180). Signed into law by President Trump on June 5, the STAR Act authorizes $150 million through fiscal year 2022 to fund various research programs, including the identification of neglected, hard-to-treat pediatric cancers; expanding the national pediatric cancer biomarker registry and providing more resources to state registries; creating a federal task force to set quality standards for survivorship care involving children and especially older adolescents; directing the Government Accountability Office (GAO) to develop recommendations for Congress and the Executive Branch on policy to tackle the financial and economic burden of cancer care on patients, including families and care-givers; and mandating appointment of at least one pediatric oncologist on the National Cancer Advisory Board.
While pediatric survivors garner the most attention, an even larger precedent was set with passage of the 21stCentury Cures Act (PL-114-255) in December 2016.Not only does the law set aside $1.8 billion through fiscal year 2023 for research on cancer that includes survivor-relevant studies in areas like cancer vaccines, palliative care, and development of new effective treatments with fewer side-effects, the law also requires the FDA to track and report on patient experience associated with a drug post-approval. This removed much of the regulatory uncertainty about use of real world evidence, which will direct clinician attention more to the long- term impact of patient exposure to treatments that remain highly toxic. In a statement on the Act, the NCCS noted this more inclusive approach to evidence generation will increase quality of life considerations as a factor both in clinical research and in the type of care patients receive during and after treatment.It’s a “step forward” for the survivorship agenda, it said.
Since the law was passed, there is an observable trend toward clinical trials centered on issues important to cancer survivors, with clinicaltrials.gov reporting 34 active or recruiting trials underway with biopharma industry involvement. Examples include a study, conducted by Dana-Farber with support fromAmgen Inc., on whether the heart medication ivabradine can be used to reduce heart rate, increase exercise duration and improve quality of life for survivors of lymphoma who received high levels of chest radiation as part of their treatment. Another study, sponsored by AbbVie Inc., is exploring the specific impacts of venetoclax, an oral agent for chronic lymphocytic leukemia (CLL), on quality of life for patients with relapsed or refractory CLL. Likewise, five big pharma companies –Roche,Pierre Fabre Group, Pfizer Inc.,Merck & Co. Inc.andAstraZeneca PLC– are participating in a retrospective European patient study using EHR data back to 2008 to examine the impact of various therapeutic strategies on improving survival prospects for metastatic breast cancer.
Elsewhere, academic medical centers and leading cancer research institutions are supporting nearly 100 US registered trials that center on wellness interventions – education, diet, exercise, cognitive reinforcement and psychosocial support – as a factor in maintaining quality of life after cancer. “As the ranks of cancer survivors grow, avoiding recurrence and the incidence of secondary cancers is going to be more important as an indicator of medical progress,” Dr. Jeffrey Meyerhardt, clinical director of Dana-Farber’s Gastrointestinal Cancer Center, tellsIn Vivo.“At Dana-Faber we are committed to research on how adherence to lifestyle factors affects outcomes in our patients with colorectal cancer, with survivor studies underway covering not only the effects of physical activity, weight change, diet and smoking but also on whether taking aspirin or COX inhibitor drugs (celecoxib) may limit recurrence, the latter in a trial we have underway with the NCI.”Meyerhardt contends there are insights still to come on the ways lifestyle and diet shape the evolution of malignancies – “it’s still the big unknown in cancer overall and I expect researchers’ interest in this area of inquiry is going to expand massively in the next few years.”
Looking ahead, the next phase of survivorship research is largely self-evident: cancer remains disproportionately a disease of the aged.According to the NCI, by 2040, half of all cancer survivors will be age 75 or older, a trend likely to accentuate the adverse treatment effects of cancer care while complicating efforts to address other, non-cancerous conditions associated with aging. In its fiscal year2019 budget request, the NCI has designated as a priority in research funding the development of new treatments that cause fewer adverse effects – in other words, “to identify factors causing or increasing susceptibility to the harmful effects of cancer and its treatment and to develop interventions to reduce or prevent their occurrence.” In addition, NCI’s National Clinical Trials Network (NCTN)has a commitment to increase the number of sponsored trials aimed at older cancer patients, particularly those with other existing health conditions such as heart disease or diabetes. The goal, according to the 2019 budget plan, is to help oncologists develop ”age-appropriate treatment plans” and guide decisions on resources and programs necessary for adultcancer survivors in long-term recovery.
Why is all this research important? Because without it, an effective clinical and institutional response – one capable of helping cancer survivors where it counts – won’t happen.“Stakeholders with different motivations and incentives must be convinced of the need to change before change can take place,” Meyerhardt says. “Only good evidence produced through collaborations across disciplines can do that.”
In a recent discussion paper, ASCO took an inventory of challenges to implementing a survivorship care program. It identified four: (1) limited experience of providers in working collaboratively across practice disciplines, as well as time and resource constraints in meeting the complex, multiple needs of cancer survivors; (2) patient indifference and/or lack of awareness about follow-up care once a cancer is “cured,” including fears of cancer recurrence that inhibit active engagement with providers; (3) patient difficulties in navigating a burdensome care delivery system and provider incentives that reward silo thinking and limit compensation for positive health outcomes; and (4) the high cost of treatment and restrictions on access and coverage to insurance, especially for screening, wellness and preventive measures important to a survivorship care plan.
ASCO’s answer to these four challenges is fairly conventional, focusing on better messaging to patients and more education in the provider community on the importance of an integrated SCP; expanding research to help identify gaps in the rehabilitation and follow-up care essential to better patient outcomes; and more data interoperability so that SCPs and other multi-faceted care plans can be shared electronically across the health delivery system. Experts interviewed byIn Vivonoted that the big unresolved issue is the variation in attitude and commitments to survivorship care: the effectiveness of that care depends on a mix of human capital and financial factors, reinforced by the clinical reality that cancer is not a single disease but a collection, whose severity and symptoms express differently in individual patients. Hence the willingness – and ability – of patients to take an active interest in their condition is critical; it cannot be forced.
A conclusion reached by many researchers is that making survivor care more relevant to each patient demands a more organized approach to risk assessment – where should that care be directed to secure the best outcome? ACS, together with ASCO and professional practice groups like the Oncology Nursing Society are working on a number of risk-stratified care protocols for various cancers, to better anticipate the late and long-term effects a patient might expect from their specific exposures to cancer treatment, and to go back and re-evaluate whether such approaches can be changed to minimize those impacts for future cancer patients.
According to the ACS’ Katherine Sharpe, “The work reinforces our position that attention we give to cancer survivors helps raise the boat for everyone, given the number of co-morbidities that attach to this population.Stratifying the level of risk for cancer patients susceptible to future heart problems from chest radiation will increase the level of knowledge in CVD as well – there is merit in sharing these insights across disciplines.”
Nevertheless, an increasing number of survivorship advocates contend the solution requires more attention to the fundamentals of health care financing and delivery. Says Dr. Mark Goldberg of the ACS, “Our cancer statistics show that, while we have an increasing number of survivors, there should be a lot more of them.”The reason behind the discrepancy, he contends, points in one direction: lack of access for patients to the right care, at the right time, for their condition.“Because of this, we have persistent disparities on outcomes between groups, driven not only by age, race and gender but by inequalities across the board, with patients who cannot get transportation to the clinic because of money or social isolation, who have no insurance or limited coverage so that basic preventive measures like cancer screening is paid entirely out of pocket. If we can start by tackling these fundamental challenges to access, the easier our task as providers will be in raising the number of survivors to a level commensurate to all the scientific progress we’ve made in treating cancer.”
This perspective, founded on decades of study on population health and its social determinants – the world as it is – is winning credence in the cancer community, which has traditionally followed a narrower path to public engagement, one centered on unquestioning professional and specialist expertise. Symbolic of the shift is the ACS July 13 announcement of a new national cancer control plan with targets for mortality reduction up to 2035. The call is for joint action by government, providers, patients, academia and industry to build on what is already known about cancer with initiatives to address disparities in care; prevention, screening and early detection; and research, not just on new treatments but in adjacent care segments such as survivorship too.
In the first of a series of papers to be published inCA: A Cancer Journal for Clinicians, a team led by ACS chief medical and research officer Otis Brawley cites “ensuring equal and full access to the combination of preventive and therapeutic measures already proven effective” as the plan’s principal goal, noting further that “the statistics demonstrate our obligation to deliver the fruits of already completed research to all Americans.”
It is a promise founded on a premise:that many more cancers survivors will be around to see it kept.
In Vivo: strategic insights for life sciences decision-maker...
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