Impact of Immune-Related Adverse Events on Checkpoint Inhibitor Consolidation Therapy in Stage III NSCLC

Conference Correspondent

Consolidation checkpoint inhibitor therapy for up to 1 year following chemoradiation (CRT) is a current standard of care for patients with inoperable stage III non–small-cell lung cancer (NSCLC). However, immune-related adverse events (AEs) can preclude some patients from completing the full year of consolidation checkpoint inhibitor therapy. Retrospective studies of patients with stage IV NSCLC who were treated with consolidation checkpoint inhibitor therapy, and who experienced immune-related AEs, generally receive fewer cycles of consolidation checkpoint inhibitor therapy with no significant detriment in terms of efficacy.

Researchers evaluated the association between immune-related AEs and efficacy outcomes from the HCRN LUN 14-179 study, a single-arm phase 2 trial of consolidation pembrolizumab following concurrent CRT in patients with unresectable stage III NSCLC. In this trial, eligible patients with stage III NSCLC who did not progress after completion of CRT received pembrolizumab 200 mg intravenously (every 3 weeks) for up to 1 year. Demographics, disease characteristics, and number of cycles of pembrolizumab received were reported in patients who had any-grade immune-related AEs, except pneumonitis that included grade ≥2 (Group A) and those without immune-related AEs (except grade 1 pneumonitis) (Group B).

A total of 92 patients were eligible for efficacy analysis. These patients were enrolled in the study from March 2015 to November 2016. The 4-year overall survival estimate for all patients is 46.2%. Any-grade immune-related AEs (except grade 1 pneumonitis) (N = 37 patients) included pneumonitis (19%), hypothyroidism (14%), hyperthyroidism (11%), increased creatinine (5%), elevated transaminases (3%), and colitis (3%). Grade ≥2 immune-related AEs (N = 32 patients) included pneumonitis (19%), hypothyroidism (11%), and colitis (3%).

The median number of pembrolizumab cycles received in Group A and Group B patients were 9 and 14, respectively (P = .15). Four-year efficacy end points in Group A and Group B were time to metastatic disease, 35% versus 41%, respectively (P = .83); progression-free survival, 28% versus 29%, respectively (P = .97); and overall survival, 44% versus 48% (P = .99), respectively.

Researchers concluded that, despite receiving fewer cycles of consolidation pembrolizumab, patients with stage III NSCLC who experienced any-grade immune-related AEs, excluding grade 1 pneumonitis, did not have significantly reduced efficacy outcomes.

Reference

  • Shukla N, Althouse SK, Sadiq AA, et al. The association between immune-related adverse events and efficacy outcomes with consolidation pembrolizumab after chemoradiation in patients with stage III non-small cell lung cancer: an analysis from HCRN LUN 14-179. J Clin Oncol. 2020;38:suppl (abstract 9032).
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Last modified: November 5, 2020

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