(P-533) PD-1 Immune Checkpoint Inhibitors and Serious Immune-related Adverse Events

Background: Randomized controlled trials (RCTs) suggested the risk of immune-related adverse events (irAEs) following the use of programmed cell death-1 (PD-1) inhibitors. While the Asian population is underrepresented in RCTs, the safety of PD-1 inhibitors among Asians can be different due to the higher prevalence of epidermal growth factor receptor mutation and hepatitis B virus infection.

Objectives: To estimate the incidence of serious irAEs and their predictors following PD-1 inhibitor use in South Korean patients with non-small cell lung cancer (NSCLC).

Methods: We identified 2,963 patients treated with PD-1 inhibitors as second-line or above therapy for stage ≥ IIIB NSCLC from a nationwide healthcare database of South Korea. Patients were followed from PD-1 inhibitor initiation with the 1-year exposure risk window. The outcome was defined as simultaneously receiving a pre-defined diagnosis for potential irAEs and corticosteroids for ≥ 14 days. Cumulative incidence of irAEs was estimated using a sub-distribution hazard model where death was treated as a competing risk.

Results: The 1-year cumulative incidence of serious irAEs was 5.6% (95% confidence intervals: 4.7%-6.6%). Subgroup analysis showed that PD-1 inhibitor users with the underlying respiratory disease had an increased risk of irAEs than those without (6.1% vs. 4.0%; Gray’s test P-value, 0.01). PD-1 inhibitor users with the autoimmune disease had a slightly higher incidence of irAEs than those without (7.7% vs. 5.4%; Gray’s test P-value, 0.19).

Conclusions: The incidence of serious irAEs in this Asian lung cancer cohort was largely consistent with the findings from RCTs. Patients with underlying respiratory or autoimmune diseases require vigilant surveillance and preventive strategies to manage potential irAEs.