Nivolumab vs Pembrolizumab
The study also evaluated the use of nivolumab and pembrolizumab, including which line of therapy, prior therapies used, and which agent was chosen, though reasons for their use were not captured.
Platinum doublet chemotherapy was the most frequently used regimen immediately prior to anti–PD-1 therapy. The first PD-1 inhibitor to be used during the disease course was nivolumab among 93% of patients, and an additional 3.4% received nivolumab in combination with another therapy.
The uptake of pembrolizumab, which was first approved in NSCLC 7 months after nivolumab, was comparably much lower, at 3.2%. The study did not, however, include data from the period after the FDA expanded pembrolizumab’s indication to include first-line therapy among patients with PD-L1 expression greater than 50% or in combination with chemotherapy.
“We were particularly struck by how quickly clinicians adopted an entirely new therapy class. In many cases, immunotherapies were supplanting therapies that had been used for years, even though no head-to-head data were available. It underscores just how excited clinicians were to use them,” Dr Abernethy said.
Future Uses for Immunotherapy
As the observation period progressed, the use of nivolumab and pembrolizumab changed: the agents were more often used in the second-line setting rather than subsequent lines. Dr Abernethy noted that the study only included the first 12 months of use after the FDA approval for PD-1 inhibitors in NSCLC. Their use has, however, continued to evolve, which is evidenced by expanded indications for pembrolizumab and additional immunotherapy approvals, such as atezolizumab.
“We expect a considerable increase in PD-L1 expression testing rates associated with patients that initiate immunotherapy,” Dr Abernethy said, highlighting that reasons for this include an increase in use of next-generational sequencing and targeted biomarker testing, the recent approval of pembrolizumab for patients with microsatellite instability, and that first-line use of pembrolizumab monotherapy requires high PD-L1 expression.
Dr Abernethy also noted that there is likely to be an increase in the use of immunotherapies in earlier treatment lines and in combination with other agents.
The findings from this study suggest that some clinicians are using immunotherapies in the types of patients not included in clinical trials. Dr Abernethy said that “as doctors at the proverbial bedside, we have to do the right thing for the patient sitting in front of us — which often means generalizing results from the clinical trial to unique clinical circumstances, trying to best blend maximizing therapeutic potential while limiting harm.”
Though the initial findings of the collaboration may not have a major effect on treatment decisions in the community, Dr Abernethy highlighted that it shows the wide variations in practice.
“Future studies with the collaboration between the FDA and Flatiron will focus on outcomes. For example, differences in survival for older patients treated with immunotherapy, or what happens when a biomarker test is conducted with an FDA-approved companion diagnostic or not,” Dr Abernethy said.
- Flatiron Health and the FDA embark on cancer research collaboration [news release]. New York: BusinessWire; May 25, 2016. https://www.businesswire.com/news/home/20160525005123/en/Flatiron-Health-FDA-Embark-Cancer-Research-Collaboration. Accessed January 18, 2018.
- Khozin S, Abernethy AP, Nussbaum NC, et al. Characteristics of real-world metastatic non-small cell lung cancer patients treated with nivolumab and pembrolizumab during the year following approval. Oncologist. 2018;22:1-9. doi: 10.1634/theoncologist.2017-0353