Pembrolizumab for all

Abstract

The current approval indications for pembrolizumab are complex, reflecting the inclusion criteria of numerous clinical trials that led to approvals. Here we argue that allowing the use of pembrolizumab to any advanced solid tumor in any tumor type in any line of therapy for a fixed duration may be preferable to the current assortment of indications. The aggregate response rate in landmark clinical trials for approved indications of pembrolizumab is low and even lower in real-world populations. Due to heterogeneity of response to checkpoint inhibitors and limited predictive biomarkers, there are subsets of patients without approved indications for pembrolizumab that may have response to checkpoint inhibitors. The current regulatory framework of numerous overlapping clinical trials leading to complex approval indications is redundant and inefficient. We conclude that giving pembrolizumab in any metastatic solid tumor in any setting may lead to better outcomes with minimal increase in cost. Randomized clinical trials should focus more on optimal duration of treatment based on tumor type and initial response to checkpoint inhibitors.

Keywords: Biomarker; Health Policy; Immunotherapy; Oncology drug approval; PD-L1.

Fig. 1

Annual sales (US$) of PD-1/PD-L1 inhibitors approved by the FDA Numbers are based on 2021 Q3 10-Q reports (Keytruda, Imfinzi, and Opdivo) or 2020-2021 company reports (Tecentriq, Libtayo). Sales data is not reported for Bavencio (approved in 2021). Cost of fixed dose pembrolizumab is $5,487 based on list price and Pricing Transparency Report by Merck