Immune-related Adverse Effects Associated with Programmed Death-1 Inhibitor Therapy in the Treatment of Non-Small Cell Lung Cancer: Incidence, Management, and Effect on Outcomes.

Abstract

The programmed death 1 (PD-1) inhibitors may improve survival outcomes of non-small cell lung cancer (NSCLC) patients but are associated with immune-related adverse effects (IRAEs). Management of IRAEs may include immunosuppression (ie, corticosteroids), but there is concern that this may affect efficacy. This study evaluated the influence of IRAEs and immunosuppression for IRAEs on survival outcomes of NSCLC patients treated with PD-1 inhibitors (pembrolizumab and nivolumab). We retrospectively examined data from Kaiser Permanente Southern and Northern California members diagnosed with NSCLC who received a PD-1 inhibitor from March 1, 2011 to September 30, 2016. Our primary goal was to evaluate the effects and management of IRAEs on survival with PD-1 inhibitors. Electronic database records were used to identify the occurrence of IRAEs, medication utilization, and death. Cox proportional hazard models were used to evaluate variables for association with increased risk of death. A total of 662 patients were included in the study (median age = 68 years) (interquartile range 61-74). IRAEs were identified in 18% of patients, of which 62% received immunosuppression. Median overall survival was 10 months (interquartile range = 4 months to not reached). Adjusting for covariates, use of immunosuppression during PD-1 inhibitor treatment was not associated with a significantly higher risk of death (hazard ratio = 1.04, 95% confidence interval = 0.84-1.29), whereas corticosteroid use before initiating PD-1 inhibitor therapy was (hazard ratio = 1.48, 95% confidence interval = 1.14-1.91). In a large, real-world cohort from an integrated healthcare system, use of corticosteroids prior to PD-1 inhibitors was associated with worse survival outcomes, whereas concomitant treatment was not.