Highlights include the emerging role of real-world evidence
in oncology and the impact of Medicaid expansion
on racial disparities in cancer care
The theme of the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, “Caring for Every Patient, Learning From Every Patient,” resonates well with our mission at Flatiron Health. We constantly strive to define how the journey of every cancer patient can contribute to the development of evidence to benefit cancer patients.
For much of my career, treatment and regulatory decisions were based largely on data obtained from clinical trials. While the “art of medicine” has always involved tailoring treatment approaches to individual patients, the evidence source was the prospective clinical trial, and so-called observational data was viewed as second-class, relegated to the realm of “hypothesis generation.” Slowly but surely, the medical landscape is witnessing a transformation in this approach and attitude, and the needle is now moving forward. The 21st Century Cures Act, signed into law in December 2016, included a mandate to develop an approach for evaluating real-world evidence (RWE) for regulatory decisions — paving the way for the FDA’s recent draft framework to further advance the use of real-word evidence.
This sea change, and Flatiron’s essential role, is also reflected in our growing presence at the premier international oncology meeting in the world — the ASCO Annual Meeting — which draws 40,000+ global oncology professionals. This year we are proud to have 16 accepted presentations featuring Flatiron data at ASCO 2019, many in collaboration with our partners, including one — of only four abstracts (out of 7,000+ submissions) — selected to be presented during this year’s Plenary session.
Below are some highlights of our research that will be presented at this year’s meeting. Collectively, the presentations feature our broad impact, with Flatiron data enabling insights that inform the design of clinical trials, contribute to our understanding of the use of biomarkers and outcomes in routine clinical care, and help evaluate national policies that affect cancer patients. This latter effort is especially exciting, as it represents the commitment of our Flatiron colleagues to address issues of societal importance, such as healthcare disparities.
Clinical Trial Design
By leveraging the de-identified real-world information on patient characteristics and treatment patterns in our databases, one of our studies aimed to answer two key questions: how generalizable are clinical trial results that enroll patients in narrowly defined controlled settings for non-trial patients who are cared for in the real world? And, are treatments used as comparative reference (i.e., control arms) in randomized clinical trials of new drugs relevant to the standards of care used in the real world? A team of Flatiron researchers found that, while generalizability of clinical trials to real-world populations is reasonably high, the treatments that are used as controls in clinical trials are often a poor reflection of actual care received in practice. These observations suggest that real-world data can be used to inform the design of future clinical trials and ensure the results are generalizable and relevant to real-world treatment decisions.
A major topic of national discussion over the past few years has been whether our current clinical trial eligibility criteria are too restrictive, yet there are scant data on how loosening certain criteria might impact the results of clinical trials. Patients with kidney or liver dysfunction are often excluded from clinical trials, because of concern that they would not tolerate treatment, or perhaps interpretation of results would be complicated. A study in collaboration with the U.S. Food and Drug Administration, the National Cancer Institute, and Flatiron explored the outcomes of patients treated with immune checkpoint inhibitors (ICIs) across multiple cancers with varying levels of baseline kidney and liver dysfunction. This study indicated that while baseline kidney function did not impact survival in patients treated with ICI, patients had progressively poorer outcomes with worsening baseline liver dysfunction. These results suggest that clinical trials of ICIs should reevaluate exclusion of patients based solely on underlying kidney disease.
Biomarkers and Patient Care Insights
The identification of biomarkers to identify which patients with lung cancer will respond to treatment with PD1/PDL1 inhibitors is a major scientific effort worldwide. The Flatiron Health-Foundation Medicine Clinico-Genomic Database (CGDB) is proving to be a growing resource for examining predictive biomarkers (see our recent paper in the Journal of the American Medical Association that explored tumor mutational burden [TMB]). In partnership with Foundation Medicine, one of the studies to be presented at ASCO 2019 examined the combined ability of TMB and PD-L1 expression to assess the response of advanced non-small cell lung cancer (NSCLC) patients to immunotherapy. While there was no correlation between TMB and PD-L1 expression, combining the two biomarkers improved identification of real-world tumor response compared to PD-L1 expression or TMB alone—higher TMB plus higher PD-L1 was associated with a better response to immunotherapy treatment in patients with advanced NSCLC.
ROS1 gene rearrangements are a driver of a rare subpopulation of lung cancers, occurring in only a few percent of people. There is great interest in the development of targeted treatments for these patients who have limited options. Due to the rarity of these patients, it is difficult to conduct randomized clinical trials that can quickly find more effective treatments. However, the emergence of real-world data offers renewed opportunity to help such rare patient populations. Roche collaborated with Flatiron to use real-world data for an exploratory analysis of an investigational medicine, entrectinib, in ROS1+ lung cancer compared to crizotinib (the standard of care). The results to be presented at ASCO reveal that time on treatment and a progression-free survival may be longer with entrectinib, showing the potential value of real-world data to compare treatment outcomes in rare populations.
Another rare population isn’t molecular, but clinical: men with metastatic breast cancer. RWE helped provide data of the use of palbociclib in males with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer and these data will also be presented at ASCO based on a collaboration between Pfizer, IQVIA and Flatiron. Analysis of de-identified claims data and de-identified EHR-derived Flatiron data on men with HR+, HER2- metastatic breast cancer treated in combination with palbociclib in the real world, supported the FDA’s expansion of the palbociclib approval, previously only approved in women, to include men with HR+, HER2- metastatic breast cancer.
I am excited to see the nationwide Flatiron database leveraged as a unique resource for measuring the impact of healthcare policy decisions. By observing and measuring care, we are able to conduct so-called natural experiments to test the effects of new policies. Using a difference-in-differences model — a powerful technique that enables the analysis of natural experiments — to explore the impact of the Oncology Care Model (OCM) on biomarker testing and biomarker-guided therapy use in patients with lung cancer. (The OCM is a voluntary Center for Medicare & Medicaid Innovation alternative payment model pilot program which requires reporting of quality metrics and clinical outcomes in order to assess the value of care. While mandated reporting may be burdensome for oncology practices, it also has the potential to impact downstream clinical care.) Originating as a hackathon project, a team at Flatiron analyzed de-identified data from 45 OCM and 105 non-OCM clinics to measure testing rates and treatment patterns in more than 7,000 patients diagnosed with advanced NSCLC. The analysis found that while rates of biomarker testing and biomarker-guided treatment were higher among OCM practices after OCM implementation, these differences were not significant after adjusting for the global improvement in these outcomes over time. This shows the importance of carefully measuring the downstream impact (or lack thereof) of policy interventions.
Medicaid expansion, a product of the 2010 Affordable Care Act (ACA), was designed to reduce inequity in healthcare access, in part by permitting states to expand eligibility for Medicaid to a higher threshold income. One of our studies, in collaboration with investigators at Yale University, evaluated the impact of the ACA’s Medicaid expansion on racial disparities in access to cancer treatment. This abstract was selected for oral presentation at the 2019 meeting’s Plenary session. Stay tuned for a follow-up blog post describing the details of our study findings once the embargo lifts on June 2!
I am looking forward to representing Flatiron Health at ASCO 2019 — to discuss the latest developments in cancer care with oncologists, researchers, regulators, drug and diagnostic developers and patients, and to gather feedback on our research findings from these stakeholders. As our platforms evolve and clinical adoption expands, I hope to see growing impact for RWE across the spectrum of clinical trials, biomarker exploration, regulatory decision making, and most importantly patient care.