Single institution experience looking at efficacy of PD-1 inhibitors after progression on PD-L1 inhibitors or vice-versa in metastatic non-small cell lung cancer (NSCLC).

Abstract

e21726 Background: The treatment landscape for metastatic NSCLC has changed dramatically with emergence of checkpoint inhibitors (CPI). Even though all currently approved CPI target engagement of PD-1 with PD-L1 and have similar efficacy in NSCLC, there are some differences in their mechanisms of action. Current guidelines do not recommend switching to another CPI after progression of disease (POD) or toxicity on one CPI. For some patients, however, therapeutic options may be limited due to comorbidities, lack of trial prospects, performance status, or reluctance towards chemotherapy making switch to alternate CPI an attractive strategy. We report outcomes of patients who were treated with second CPI after POD on initial CPI for metastatic NSCLC between 2015 and 2019 at our institution. Methods: Data collection included demographics, clinic-pathologic factors, CPI agents, disease control rate (DCR), progression free survival (PFS), and immune-related adverse events (irAE). DCR was defined as response or stable disease based on RECIST. PFS was measured from date of initiation of CPI to POD or death. Results: Of 169 patients with NSCLC treated with CPI (median age 71 years, range 30-93), 26 received 2 lines of CPI. Two patients received first CPI as part of front line chemoimmunotherapy whereas all others received CPI alone. First CPI was PD-1 inhibitor in 20 patients and PD-L1 inhibitor in 6. DCR for first CPI was 88% and median PFS of 5 months (range: 1 –24). There were no irAE over grade 2 with initial CPI. Six patients were treated with PD-1 inhibitors after PD-L1, 16 with PD-L1 after PD-1, and 4 with an alternate agent in same class. Median PFS for 2nd CPI was 3 months (range: 1 - 36) for all patients and DCR for evaluable patients was 63% (n = 16). One patient experienced steroid-responsive grade 2 pneumonitis. Responses with either line of CPI did not correlate with PD-L1 expression. Conclusions: Our data suggests that switching from one CPI to another may be a reasonable, potentially effective option in select patient population. Prospective studies exploring this strategy is warranted.