Abstract 6743: Clinical outcomes with pembrolizumab-based therapies in relapsed/refractory NSCLC after definitive chemoradiation and durvalumab
Authors: Delasos Lukas , Wei Wei , Hassan Khaled A. , Pennell Nathan , Patil Pradnya , Stevenson James 
Published: April 2023

Background: More than 50% of patients (pts) with unresectable non-small cell lung cancer (NSCLC) experience relapsed/refractory (R/R) disease within 2 years of starting chemoradiation (CRT) and durvalumab. Based on current national guidelines, these patients are offered treatment for metastatic disease as definitive therapy is no longer feasible. Immunotherapy +/- chemotherapy is typically initiated if a driver-oncogene is absent. The addition of programmed cell death protein-1 (PD-1) antibody pembrolizumab to chemo has resulted in improved progression-free survival (PFS) (8.8 vs 4.9 mos) and overall survival (OS) (69.2% vs 49.4% 12-mos OS) compared to chemotherapy alone. Although this treatment strategy has been incorporated for R/R NSCLC, there remains a paucity of data regarding its efficacy within this population. Here we present clinical outcomes data with pembrolizumab-based regimens for R/R NSCLC following definitive CRT and durvalumab.

Methods: This was a retrospective analysis of pts treated between January 2016 to November 2022 at the Cleveland Clinic Foundation in Cleveland, OH. Eligibility criteria included pts age ≥ 18 years with unresectable NSCLC who had received definitive CRT and durvalumab consolidation followed by pembrolizumab for R/R disease. The primary objective was to estimate OS and PFS in this distinct cohort and to compare these findings to historical outcomes. Secondary objective was to compare OS and PFS between specific groups including age, sex, smoking history, combined chemo, histology, KRAS-mutation, and PD-L1 expression. OS and PFS were estimated by Kaplan-Meier method and compared using log rank test.

Results: 62 pts were identified, of whom 50 met full eligibility criteria and were included for data analysis. Median follow-up time was 11.3 months (0.7 - 38.2 mos). Median OS was 10.6 months (95% CI; 7.9 mos - NA) with a 1-year OS rate of 48% (95% CI; 35 - 67%). Median PFS was 6.1 months (95% CI; 4.8 - 9.9 mos) with a 1-year PFS rate of 26% (95% CI; 16-45%). Current smokers had significantly better median OS and PFS rates as compared to former smokers (NA vs 10.5 and 9.9 vs 6.0 mos, respectively; P = 0.036 and 0.028). An OS benefit in pts who received chemo with pembrolizumab (median OS 12.9 vs 6.0 mos) was noted but was not statistically significant. No other statistically significant difference was detected.

Conclusion: Patients with R/R NSCLC after definitive CRT and durvalumab consolidation represent a distinct cohort with apparent inferior outcomes as compared to those with de novo stage IV disease when treated with pembrolizumab-based therapies. Although improved survival was observed with the addition of chemo to pembrolizumab, further investigation is warranted to optimize treatment strategies for this patient population. Given the limited sample size of our analysis, larger studies with matched real-world treatment cohorts are planned.

Citation Format: Lukas Delasos, Wei Wei, Khaled A. Hassan, Nathan Pennell, Pradnya Patil, James Stevenson. Clinical outcomes with pembrolizumab-based therapies in relapsed/refractory NSCLC after definitive chemoradiation and durvalumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6743.