While immunotherapy with programmed death receptor 1 (PD-1) inhibiting antibodies has revolutionized the treatment of non-small cell lung cancer (NSCLC), use of these agents comes at the cost of potential serious immune-related adverse events (irAEs). In melanoma, development of cutaneous irAEs, such as rash and vitiligo, during treatment with PD-1 inhibitors has been shown to be associated with survival benefit, suggesting that early onset of irAEs may predict treatment outcomes. However, in NSCLC, the predictive value of immunotherapy-related toxicity as a clinical marker for efficacy to PD-1 inhibition is unknown. A multi-institution retrospective study investigated the relation between the development of irAEs and efficacy of PD-1 inhibitors in 134 patients with advanced or recurrent NSCLC who received second-line treatment with nivolumab. The primary outcome for this analysis was progression-free survival (PFS) according to the development of irAEs in a 6-week landmark analysis.
Immune-related adverse events were observed in 51% of patients evaluated in this study, including grades 3 or 4 events in 9% of the patients, and 18% of patients required systemic corticosteroids for irAEs management. Development of irAEs was also indicative of response, as the overall response rate was higher in patients with irAEs than in patients without (52.3% vs 27.9%; P = .02). Median PFS as estimated in the 6-week landmark analysis was 9.2 months for patients who developed irAEs compared to 4.8 months for patients who did not (P = .04). Median estimated overall survival (OS) was not reached in patients with irAEs versus 11.1 months in patients without irAEs (P = .01). Similar results were found with 4-week and 8-week landmark analyses. In addition, a multivariable analysis also demonstrated positive association between the development of irAEs and both PFS (HR 0.525, P = .03) and OS (HR 0.282, P = .003). The greatest association between irAEs and outcomes was seen in patients who developed skin or endocrine-related irAEs.
The authors concluded that these results indicate that the development of irAEs is a robust positive predictor of long-term outcomes for anti-PD-1 therapy in advanced NSCLC. However, further studies analyzing this link with larger patient samples and longer follow-up are needed.