P2.04-09 Immune-Related Adverse Events in Advanced Non-Squamous NSCLC Patients Treated with Upfront Checkpoint Inhibitors Combination

Abstract

Immune-related adverse events (IRAE) are a unique set of adverse events caused by checkpoint inhibitors due to enhanced activation of the immune system. IRAEs can virtually affect any organ system and have been responsible for significant morbidity, treatment delay, treatment discontinuation, and even death. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of IRAEs when checkpoint inhibitors were utilized as first-line in combination with chemotherapies in non-squamous non-small cell lung cancer (NSCLC) patients. We systematically conducted a literature search using PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019. Phase 3 RCTs that mention IRAEs as adverse effects were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q -statistic. Random effects model was applied. 2785 patients with advanced non-squamous NSCLC from 5 RCTs (Keynote – 021,189, IMpower – 130, 132 and 150) were eligible. The study arm used standard chemotherapy regimens in combination with pembrolizumab or atezolizumab while control arm utilized only standard chemotherapy regimens. The randomization ratio was 2:1 in IMpower-130 and Keynote-189 studies and 1:1 in other studies. The RR of all-grade side effects were as follows: hypothyroidism, 3.82 (95% CI: 2.14 – 6.80, p < 0.0001); hyperthyroidism, 2.58 (95% CI: 1.32– 5.04; p = 0.005); pneumonitis, 2.62 (95% CI: 1.58– 4.32; p = 0.0002); hepatitis, 3.75 (95% CI: 1.23 – 11.50, p = 0.02); colitis, 4.82 (95% CI: 1.67– 13.90; p = 0.004); and pancreatitis, 2.35 (95% CI: 0.75–7.41; p =0.14). The RR of high-grade side effects were as follows: hypothyroidism, 2.93 (95% CI: 0.62 – 13.74, p = 0.17); hyperthyroidism, 2.32 (95% CI: 0.37– 14.71; p = 0.37); pneumonitis, 1.65 (95% CI: 0.80– 3.41; p = 0.18); hepatitis, 4.14 (95% CI: 1.05 – 16.33, p = 0.04); colitis, 3.31 (95% CI: 1.02– 10.77; p = 0.05); and pancreatitis, 1.44 (95% CI: 0.29– 7.13; p = 0.65). Patients on combined chemoimmunotherapy experienced a significant increase in all grades of hepatitis and colitis with a relative risk of 4.14 for grade 3 and 4 hepatitis. They also contributed to all-grade hypothyroidism, hyperthyroidism and pneumonitis. These toxicities have significant impact on patients’ quality of life, ultimately affecting patients’ compliance. A timely intervention with proper supportive care is necessary.