Association of Immune-Related Adverse Events and Efficacy Outcomes With Consolidation Pembrolizumab After Chemoradiation in Patients With Inoperable Stage III Non-Small-Cell Lung Cancer.

BACKGROUND

Many patients with non-small-cell lung cancer (NSCLC) treated with immunotherapy experience immune-related adverse events (irAEs). Patients with metastatic NSCLC who receive checkpoint inhibitors (CPI) and experience irAEs generally receive fewer cycles of CPI without decreased efficacy. However, the association between irAEs and efficacy outcomes in patients with locally advanced NSCLC treated with curative intent with CPI after chemoradiation has never been reported. Here we report a retrospective analysis of the association between irAEs and efficacy outcomes from the Hoosier Cancer Research Network (HCRN) LUN 14-179 single-arm phase 2 trial of consolidation pembrolizumab after chemoradiation in patients with stage III NSCLC.

PATIENTS AND METHODS

A total of 92 eligible patients were enrolled from March 2015 to November 2016. Demographics, disease characteristics, and number of pembrolizumab cycles received were reported in patients with and without irAEs. Chi-square test was used for comparisons for categorical variables and Wilcoxon test for continuous variables. The Kaplan-Meier method was used to analyze time to metastatic disease or death (TMDD), progression-free survival (PFS), and overall survival (OS). A log-rank test was used to compare groups.

RESULTS

Any grade irAEs occurred in 55.4% of patients. There was no significant difference in number of pembrolizumab cycles received, TMDD, OS, or PFS in patients with and without irAEs. Patients who discontinued pembrolizumab early because of irAEs received significantly fewer cycles of pembrolizumab (5 vs 15, P = .0016) without a significant difference in TMDD, PFS, or OS. Similarly, patients who received immunosuppressive therapy received fewer numbers of cycles of pembrolizumab (4 vs 16, P < .001) without significantly reduced TMDD, PFS, or OS.

CONCLUSION

irAEs due to pembrolizumab, regardless of grade or number of irAEs, were not associated with decreased efficacy outcomes. Furthermore, early discontinuation of pembrolizumab because of irAEs and/or treatment of irAEs with immunosuppressive therapy was not associated with a decrease in treatment efficacy.