Clinical outcomes of patients with non-small cell lung cancer (NSCLC) receiving chemotherapy after immune checkpoint blockade.

Abstract

9082 Background: Objective response rates (ORR) to chemotherapy beyond the first-line for advanced NSCLC are low (5-10%). Pre-clinical studies suggest that some chemotherapies may act, in part, through immune mediated mechanisms. Additionally, results from phase I/II studies of chemotherapy combined with immune checkpoint inhibitors (ICIs) suggest high response rates ( > 50%) and potential synergy. It is unknown whether chemotherapy is more efficacious when given after ICIs. Methods: We reviewed demographics, imaging, treatment history, and clinical course for all patients at our institution with a diagnosis of metastatic NSCLC who received at least one dose of nivolumab, pembrolizumab, atezolizumab, or durvalumab prior to December 8, 2016. Patients who received any subsequent chemotherapy were included for analysis. Objective response was determined by RECIST v1.1, and date of progression was determined radiographically or clinically (treatment discontinuation with documented clinical deterioration). Results: 145 patients received at least one dose of any ICI, and 38 patients received subsequent chemotherapy. The median age was 68 years (range 44-88). Six chemotherapy-naïve patients received carboplatin + pemetrexed +/- bevacizumab. There were 3 partial responses (PR) including one exceptional response that is ongoing after 2 years. Among 32 chemotherapy non-naïve patients, the median number of prior chemotherapy regimens was 2 (range 1-6). Post-ICI chemotherapy included docetaxel + ramucirumab (n = 12), vinorelbine (n = 7), gemcitabine-based chemotherapy (n = 6), carboplatin doublets (n = 4), pemetrexed + bevacizumab (n = 2), and paclitaxel (n = 1). Six patients had documented poor performance status and died within 1 month of starting treatment. The ORR was 25% (1CR, 7PR), median time to progression was 116 days, and 9 patients (28%) experienced stable disease (SD) or better lasting > 150 days. Exceptional responses occurred across regimens. Nine patients received a further line of chemotherapy, with 3 ongoing PR or SD lasting > 100 days. Conclusions: For NSCLC, chemotherapy response rates may be higher when administered after an ICI.