Incidence, Risk Factors, and Effect on Survival of Immune-related Adverse Events in Patients With Non-Small-cell Lung Cancer

Abstract

Background: The risk factors for immune-related adverse events (irAEs) remain undefined. Recently, a correlation between irAEs and clinical benefit was suggested. We examined the risk factors for irAEs and their effect on survival in patients with non-small-cell lung cancer (NSCLC) who had received immunotherapy.

Patients and methods: We performed a retrospective review of patients with NSCLC treated with single-agent immunotherapy at our institution. irAEs were determined by treating physician diagnosis. A landmark analysis was performed at 3 months using log-rank tests and the Bonferroni method.

Results: irAEs occurred in 27 of 91 patients (30%). The median overall survival (OS) for patients with irAEs was longer than that for patients without (24.3 vs. 5.3 months; hazard ratio, 2.75; 95% confidence interval, 1.54-4.92; P < .001). However, a landmark analysis of patients after 3 months of treatment revealed no difference in OS between patients with and without irAEs. No increased risk of pneumonitis was seen in patients with previous thoracic radiotherapy, although these patients had shorter survival (4.2 vs. 9.7 months; P = .004). Radiotherapy after the initiation of immunotherapy (n = 15) did not increase the risk of irAEs or pneumonitis; however, these patients had improved OS (17.3 vs. 6.0 months; P = .016).

Conclusion: The development of irAEs did not significantly correlate with survival when controlling for the duration of therapy in a landmark analysis. We found no increased risk of pneumonitis or irAEs in patients who had received radiotherapy. Radiotherapy before immunotherapy was associated with shorter survival, and radiotherapy after immunotherapy was associated with improved survival.

Keywords: Immune checkpoint inhibitor; Immunotherapy; NSCLC; Toxicity; irAEs.

Figure 1

Swimmer’s Plot of Time to Immune-related Adverse Event (irAE), Duration of Treatment, and Outcome. Patients WhoDeveloped irAEs > 3 Months Had Improved Overall Survival (OS) Compared With Those Who Had Developed irAEs Within the First 3 Months (P < .001 With Bonferroni Correction). However, a Landmark Analysis of Patients Still Receiving Treatment at 3 Months Revealed No Differences in Overall Survival Between Patients With and Without irAEs. One Patient (Asterisk) Was Administered a Different Immunotherapy Treatment (Programmed Cell Death-1) After Stopping Initially and Developed an irAE

Figure 2

Kaplan-Meir Curves for (A) Survival of Patients Who Had Developed Immunotherapy-related Adverse Event(s) (irAE)(P < .001), Including Specifically Thyroid irAE (C; P =.018). In a Landmark Analysis Controlling for Duration of Therapy, Overall Survival Was Not Significantly Different in Patients Who Had Received an Immune Checkpoint Inhibitor (ICI) for > 3 Months With or Without irAEs Overall (B; P =1.00, With Bonferroni Correction); However, Thyroid irAEs Remained Significantly Associated With Survival (D; P =.0296)