Flatiron, Foundation Medicine study points to real-world data’s utility in oncology

In Clinical Trials by Barbara Jacoby

By: Alaric DeArment

From: medcitynews.com

Data published in JAMA on lung cancer patients treated with immunotherapy drugs, gleaned from EHRs and genomic sequencing, backs up clinical trial data and validates clinico-genomic database, the companies said.

Patients with non-small cell lung cancer whose tumors carry high mutation burden and are treated with immune checkpoint inhibitors show prolonged responses to treatment and survival. That’s already known from clinical trials, but according to a newly published study among thousands of patients, there’s also real-world data to back it up.

The study, conducted by Foundation Medicine and Flatiron Health – both subsidiaries of Swiss drugmaker Roche – was published Tuesday in the Journal of the American Medical Association. It linked clinical data from electronic health records for 28,998 patients from 275 oncology practices in Flatiron Health’s network with comprehensive genomic profiling data from Foundation Medicine’s FoundationCORE database, zeroing in on 4,064 patients with NSCLC.

In particular, the study corroborated clinical trial data showing that high tumor mutational burden – as measured by number of mutations per megabase – is associated with longer duration and improved overall survival of response among patients who receive PD-1 and PD-L1-targeting immune checkpoint inhibitors. Among the 1,290 patients treated with one of those drugs a tumor mutational burden of 20 or more was associated with a significantly improved median overall survival – 16.8 months, compared with 8.5 months among those with lower burdens. Higher-burden patients also received therapy for a longer amount of time, 7.8 months versus 3.3 months for the lower-burden group, while their respective clinical benefit rates were 80.7 percent and 56.7 percent. Mutational burdens were higher among patients with a history of smoking, who comprised more than three-quarters of those in the study, and lower among those with an alteration of the gene EGFR, ROS1, ALK or RET than among those without.

The checkpoint inhibitors patients received included PD-1 inhibitors like Merck & Co.’s Keytruda (pembrolizumab) and Bristol-Myers Squibb’s Opdivo (nivolumab) and PD-L1 inhibitors like Roche’s Tecentriq (atezolizumab), AstraZeneca’s Imfinzi (durvalumab) and Pfizer and Merck KGaA’s Bavencio (avelumab).

The publication “represents a major milestone in our mission to leverage regulatory-grade, real-world data to advance cancer care,” said Gaurav Singal, Foundation Medicine’s chief data officer, in a statement. “As the dataset continues to grow, we expect it will advance therapeutics development, optimize clinical trial design and execution and ultimately even support clinical decision making, enabling a more efficient way to evaluate new medicines and accelerate their availability for patients who need them.”

With respect to data being regulatory-grade, the Food and Drug Administration has taken notice and supported efforts to incorporate real-world data and evidence into decision making. In February, it renewed a collaboration with Flatiron – dating back to 2016 – focusing on how RWE can support regulatory decisions and offer insight into cancer treatment trends and clinical outcomes. The FDA issued guidelines in December for the use of RWE in the context of regulatory decisions, stating that it has already begun incorporating it. Last month, drugmaker Bristol-Myers Squibb and Concerto HealthAI announced a partnership to use real-world data and artificial intelligence in clinical trial design.