Factors Associated with Disease Progression after Discontinuation of Immune Checkpoint Inhibitors for Immune-Related...

Among patients with advanced non-small cell lung cancer (NSCLC) who discontinue immune checkpoint inhibitors (ICI) because of immune-related adverse events (irAE), post-discontinuation clinical outcomes and factors associated with disease progression after discontinuation are largely unknown.

Clinicopathologic data were abstracted from patients with advanced NSCLC who received ICI and discontinued treatment because of irAE. Factors associated with post-discontinuation progression-free survival (PFS) and post-discontinuation overall survival (OS) were evaluated.

Of 2,794 patients, 10% (N = 271) discontinued ICI because of irAE, and the median duration of ICI treatment before discontinuation for irAE was 5.9 months (range, 0.03-73.5). A longer treatment duration before discontinuation for irAE was associated with improved post-discontinuation outcomes: for patients on ICI for <3 months (N = 89), 3 to 6 months (N = 49), and >6 months (N = 133) before discontinuing for irAE, the median post-discontinuation PFS was 6.2, 13.9, and 25.8 months (P < 0.001), respectively, and the median post-discontinuation OS was 21.7, 42.7, and 86.9 months (P < 0.001), respectively. At multivariable analyses, predictors of longer post-discontinuation PFS were PD-L1 ≥ 50%, complete response/partial response (CR/PR) to treatment, and treatment duration before discontinuation between 3 to 6 months and >6 months; predictors of longer post-discontinuation OS were nonsquamous histology, CR/PR, and treatment duration before discontinuation >6 months. The use of immunosuppressive agents for toxicity management did not affect post-discontinuation outcomes.

A longer treatment duration before discontinuation, a best objective response of CR/PR, PD-L1 ≥50%, and nonsquamous histology may help clinicians identify patients who may experience long-term disease control after discontinuation of ICI for irAE.