Response rate to chemotherapy after disease progression with anti-PD-1/PD-L1 in metastatic cancer.

Abstract

e14088 Background: The checkpoint inhibitor (CPI) immunotherapy class of drugs is redefining how we treat cancer. The US FDA has approved CPI drugs as 1st, 2nd or salvage line after progression on conventional chemotherapy (CTX) for multiple cancers including melanoma, lung, bladder and other cancers. However, many questions remain regarding optimal treatment post-progression. Indeed, it has been noted that the patterns of response and relapse to CPI agents are quite different from those of standard cytotoxic agents and that response to CTX AFTER CPI may be different than in the de novo setting. The purpose of this retrospective analysis is to evaluate the activity (response rate (RR), response duration (DOR) and progression free survival (PFS)) of subsequent CTX after disease progression following treatment with CPI. Methods: In this analysis, patients (pts) were enrolled under an IRB approved waiver of consent. We identified pts treated with CPI agents between Jan, 2011 and Dec, 2018 at a multi-site community cancer program who received subsequent CTX as a result of disease progression (PD). We assessed the RECIST RR to subsequent therapy, DOR from onset of response, and PFS from the onset of post CPI CTX, identifying index lesions from the most recent pre-treatment anatomic scan. Results: A total of 47 cases satisfying the above criteria were found; 31 NSCLC, 8 melanoma, 1 SCLC, 1 GEJ, 1 gastric, 2 head/neck, 1 large cell neuroendocrine tumor, 2 bladder cancer. 25 pts had PD as best response to post-CPI CTX. 9 pts (19%) achieved a partial response (PR) with a median DOR of 99 days. 22 pts achieved a PR or stable disease (SD) for a clinical benefit (CB) rate of 47%. The median duration of CB was 92 days. Of the 9 patients who achieved PR, 5/6 had achieved response to CTX prior to CPI . The median PFS for the entire cohort was 97 days. Conclusions: While an expected RR could not be calculated in this heterogenous group of pts, the number and degree of responses suggests CPI possible “priming” that may enhance response to CTX. Post-CPI CTX may be of value and in this retrospective study of a heterogenous group of pts, responses may be more frequent than expected. A larger further study is warranted.