Checkpoint Inhibitors Improve Response to Salvage Chemotherapy in NSCLC

Pretreatment with immune checkpoint inhibitors are associated with a higher likelihood of response to salvage chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC), according to results of a new retrospective study.

“Checkpoint inhibitors are currently the standard of care for NSCLC patients in the second-line setting after chemotherapy and are used for a subset of patients with high PD-L1 [programmed death ligand 1] expression as frontline therapy,” said lead investigator Sacha Rothschild, MD, PhD, of University Hospital Basel in Switzerland, in a press release. “So far, it is unclear how to treat patients not responding to immune checkpoint inhibitors or progressing after initial response to these agents.” Rothschild will present results of the new study on May 7 at the 2017 European Lung Cancer Conference in Geneva, Switzerland.

The study was a retrospective analysis of 82 patients with stage IV NSCLC; most had adenocarcinoma (63 patients). Among all patients, 67 had been previously treated with programmed death 1 (PD-1)/PD-L1 inhibitors; 56 received nivolumab, seven received pembrolizumab, and four received atezolizumab. The remaining 15 patients served as controls for this study. All patients had been previously treated with chemotherapy, with a mean of 2.37 prior regimens among the cases and 1.93 regimens among control patients.

Patients pretreated with the immune checkpoint inhibitors had a 27% partial response rate to salvage chemotherapy, compared with 7% among control patients, for an odds ratio of 0.3 (P < .0001). Among the case patients, 51% had stable disease, compared with 53% of control patients; progressive disease was observed in 22% of cases and 40% of control patients.

Further analysis showed that a variety of other factors were not associated with response to chemotherapy; these included age, gender, number of prior chemotherapy regimens, tumor histology, smoking status, or specific salvage chemotherapy regimens.

Rothschild noted that the finding still needs to be explored in larger cohorts, and in prospective fashion, before it can be confirmed. Durations of response and toxicity outcomes also still remain to be analyzed.

“At this point we can only speculate on the reasons for better response in those pretreated with checkpoint inhibitors,” Rothschild said. “Probably the activation of the immune system by checkpoint inhibition might render tumor cells more sensitive to chemotherapy.” Another possibility is that chemotherapy may help tumor-specific immune cells to influence the tumor microenvironment.

Marina Garassino, MD, of the National Cancer Institute of Milan, commented on the study. “Although the results are preliminary, they suggest that immunotherapy can change the natural history of the disease and the microenvironment of the tumor, therefore rendering it more sensitive to chemotherapy,” she said. “This could potentially point to new areas of research and new sequences of treatment.”