Clinical Outcomes With Pembrolizumab-Based Therapies in Recurrent/Refractory NSCLC After Chemoradiation and Consolidative Durvalumab

Recurrent/refractory non-small-cell lung cancer (NSCLC) following definitive chemoradiation and consolidative durvalumab remains a distinct disease process with poorly defined treatment strategies. We retrospectively assessed outcomes associated with pembrolizumab in 50 subjects treated for disease relapse after definitive therapy. Our results demonstrate an inferior survival advantage with pembrolizumab in this cohort when compared to those with newly advanced NSCLC.Background: Often, patients with NSCLC experience recurrent/refractory (R/R) disease within 2 years of chemoradiation (CRT) and consolidative durvalumab. Despite prior immune checkpoint inhibitor exposure, immunotherapy with or without chemotherapy is typically initiated if a driver-oncogene is absent. However, there remains a paucity of data regarding the efficacy of immunotherapy in this patient population. Here, we present survival outcomes associated with pembrolizumab for R/R NSCLC. Materials and Methods: We retrospectively assessed adults with NSCLC who received pembrolizumab for R/R disease between January 2016 to Januar y 2023. Primar y objective was to estimate OS and PFS in this cohort compared to historical outcomes. Secondary objective was to compare OS and PFS among subgroups. Results: Fifty patients were evaluated. Median follow-up time was 11.3 months (2.9-38.2). OS was 10.6 months (95% CI, 8.8-19.2); 1-year OS rate 49% (95% CI, 36 -67%). PFS was 6.1 months (95% CI, 4.7-9.0); 1-year PFS rate 25% (95% CI, 15%-42%). Current smokers had significantly better median OS/PFS as compared to former smokers (NA vs. 10.5 and 9.9 vs. 6.0 months, respectively). The addition of chemotherapy demonstrated an OS benefit (median OS 12.9 vs. 6.0 months) but was not statistically significant.Conclusion: Patients with R/R NSCLC represent a distinct cohort with inferior survival outcomes when compared to those with de novo stage IV disease treated with pembrolizumab-based regimens. Based on our findings, we recommend oncologists exercise caution when considering checkpoint inhibitor monotherapy in the front-line setting for R/R NSCLC, regardless of PD-L1 expression.