P1.01-135 Salvage Chemotherapy After Immunotherapy Failure in Non-Small-Cell Lung Cancer Patients

Abstract

Objective response rate (ORR) to salvage chemotherapy (sCT) in non-small-cell lung cancer (NSCLC) patients failing upfront platinum-based doublets is limited (≈5-15%). Recently, unexpected favorable outcomes have been reported for sCT upon progression to immune checkpoint inhibitors (ICIs) as compared to historical data, with ORR observed in up to 53% and 27% in Asian and Caucasian patients respectively. Few data are available regarding prior response to ICIs and sCT performance, especially in Caucasian patients. All consecutive patients with advanced NSCLC who started ICIs at our institution from Apr 2013 to Dec 2018 were retrospectively reviewed. Patients who underwent sCT after progression to ICIs and had at least one radiological response assessment were included. ORR was calculated as the percentage of complete or partial responses according to RECIST 1.1 as best response. Survivals were estimated with Kaplan-Meier method. Correlation was assessed using Spearman’s test. Out of 283 patients included, 43 received sCT after ICIs. Among them, 29 (67%) had adenocarcinoma and 14 (37%) squamous cell carcinoma. 11 (26%) patients received sCT as second line therapy and 32 (74%) as third or more advanced treatment. sCT regimens included platinum based doublets (14; 32.5%), docetaxel or paclitaxel (20; 46.5%), and other monotherapies such as gemcitabine or vinorelbine (9; 21%). ORR to sCT was 30%. Median progression free survival and overall survival were 3.6 and 8.4 months, respectively. All patients receiving taxanes as sCT had already been treated with platinum based therapy and their ORR to sCT was 40%. ORR to upfront chemotherapy was 50%, while ORR to the last chemotherapeutic regimen prior to ICIs was 35%. ORR to sCT in pretreated patients was non-inferior to that observed in chemo-naïve ones (31% and 27%, respectively). High ORR (25%) was observed even in patients receiving sCT beyond third line. Neither response to ICIs (P=0.36) nor to prior chemotherapeutic regimens (P>0.05) were associated to the likelihood of achieving tumor response to sCT. We provide further evidence that NSCLC patients progressing to ICIs might still benefit from sCT even if heavily pretreated, regardless of sensitivity to ICIs or previous chemotherapy regimens. Further investigations are needed for uncovering bases of increased sensitivity to genotoxic agents in patients with innate or acquired resistance to ICIs and exploiting optimal treatment sequence.