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

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Abstract

Immunotherapy is a mainstay of treatment for non–small-cell lung cancer. Serious immune-related adverse events (irAEs) occur; however, their effect on survival is unclear, and no defined risks factors have been elucidated. In the present study, we found no significant effect of irAE on survival in a landmark analysis, and no increased risk of pneumonitis in patients with previous radiation.

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.

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