Immune checkpoint inhibitors have significantly reshaped the treatment landscape of advanced non-small cell lung cancer (NSCLC) in the second-line and, more recently, in the first-line setting. However, only a subset of patients achieves a durable response on immunotherapy, and it is not clear whether prior immunotherapy treatment impacts response to salvage chemotherapy.
A recent retrospective study evaluated responses to salvage chemotherapy in 73 patients with advanced NSCLC who had progressed on prior PD-1/PD-L1 inhibitors. Ten of the 73 patients had received immunotherapy as first-line treatment, while the remaining 63 patients had received immunotherapy as second-line treatment following first-line chemotherapy. Response to salvage chemotherapy was compared to response to the last chemotherapy administered before immunotherapy (LCBI).
The objective response rate (ORR) to salvage chemotherapy after immunotherapy was 53.4%, which was an improvement over responses to LCBI (34.9%; P = .03). The improved responses to salvage chemotherapy were consistent regardless of type of chemotherapy received. Patients treated with platinum-doublet chemotherapy achieved an ORR of 66.7% with salvage chemotherapy, compared to 39.5% for LCBI (P = .03). Patients who received non-platinum monotherapy achieved an ORR of 46.9% on salvage chemotherapy and 25.0% on LCBI (P = .09). Responses to salvage chemotherapy were higher in patients who had achieved partial response to prior immunotherapy compared to those who did not respond to immunotherapy (71.4% vs 51.5%; P = .31).
However, there were no differences in progression-free survival (PFS) between salvage chemotherapy and LCBI. Median PFS for patients on salvage chemotherapy was 4.2 months, compared to 4.7 months on LCBI (P = .84). The authors speculate this may be due to lack of continuity of the immunomodulatory effect of chemotherapy.
The investigators concluded that these data indicate that immunotherapy increases a tumor’s sensitivity to chemotherapy and supports a therapeutic sequence of immunotherapy followed by chemotherapy. This sequential approach is supported by other studies, including the analysis from the KEYNOTE-024 first-line trial, in which patients who received second-line chemotherapy following first-line immunotherapy had superior PFS compared to patients who received chemotherapy followed by immunotherapy. Future studies should investigate these outcomes in order to determine the optimal treatment sequence for patients with advanced NSCLC.