Very early molecular marker of tumor response to PD-1 inhibition in plasma of patients with advanced non-small cell lung cancer (NSCLC).

Abstract

3030 Background: Nivolumab shows a durable tumor response in 20 % of advanced NSCLC patients. While a PD-L1 immunohistochemistry complementary diagnostic has been approved, there is a need to identify a predictive biomarker with greater diagnostic accuracy. Methods: In an ongoing study of patients, treated with nivolumab every 2 weeks for advanced recurrent NSCLC and a known KRAS mutation in the primary tumor, liquid biopsies were taken by a simple blood draw at baseline (before treatment), 1, 2, 4, 6 and thereafter every 12 weeks until disease progression. Circulating tumor DNA (ctDNA) was extracted from cell free plasma and tested with a specific digital droplet PCR (ddPCR)-KRAS G12/G13 screenings assay (BIORAD). Mutation levels in plasma were compared with tumor response on CT scans by RECIST v.1.1. CT scans were performed at baseline and thereafter every 6 weeks until disease progression. Results: Patient characteristics are shown in table 1. In this prospective analysis specific patterns could be demonstrated in plasma ctDNA testing of KRAS mutation levels. All 4 responders showed an increase of mutant copies/ml plasma in the first week followed by a clear drop to non-detectable KRAS mutations at all CT evaluated tumor responses. The 2 non-responders however, did not show the increase in mutant copies/ml at one week and showed a gradual increase in mutant copies/ml in the following weeks. Conclusions: Specific plasma ctDNA testing seems a very promising early biomarker (1 week) for tumor response to PD-1 therapy. [Table: see text]