Upfront atezolizumab chemoimmunotherapy-associated immune-related adverse events in patients with advanced non-small cell lung cancer

Abstract

Background: Among lung cancers, non- small cell lung cancer (NSCLC) accounts for approximately 80% of cases. It is one of the leading causes of cancer related mortality in US. Atezolizumab is a humanized monoclonal antibody against the programmed cell death-ligand 1 (PD-L1) protein. We have conducted a meta-analysis to evaluate the risk of first-line atezolizumab chemoimmunotherapy- associated immune-related adverse events (IRAEs) in patients with advanced NSCLC. Method(s): PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019 were queried. Phase III 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). Random effects model was applied. Result(s): A total of 2725 patients with advanced NSCLC from four phase III RCTs were eligible. The study arm used standard chemotherapy regimens in combination with atezolizumab while control arm utilized only standard chemotherapy regimens. The RR of all-grade side effects were as follows: rash, 1.68 (95% CI: 1.13 - 2.50, p=0.01); hepatitis, 2.57 (95% CI: 1.21- 5.49; p=0.01); hypothyroidism, 6.27 (95% CI: 2.55 - 15.44, p<0.0001); hyperthyroidism, 3.95 (95% CI: 1.77- 8.78; p=0.0008); pneumonitis, 3.29 (95% CI: 1.98- 5.46; p<0.0001); and colitis, 5.02 (95% CI: 1.74-14.50; p=0.003). The RR of high-grade side effects were as follows: rash, 2.70 (95% CI: 1.20 - 6.10, p=0.02); hepatitis, 4.35 (95% CI: 1.80- 10.51; p=0.001); hypothyroidism, 3.51 (95% CI: 0.75 - 16.46, p=0.11); hyperthyroidism, 2.48 (95% CI: 0.50- 12.25; p=0.27); pneumonitis, 1.63 (95% CI: 0.72- 3.72; p=0.24); and colitis, 3.86 (95% CI: 1.19-12.53; p=0.02). Conclusion(s): Our meta-analysis showed that the addition of atezolizumab to standard chemotherapy, contributed to higher incidence of all grades of rash, hepatitis and colitis with RR of 4.35 for grade 3 and 4 hepatitis. They also increased the risk of all-grade hypothyroidism, hyperthyroidism and pneumonitis. Timely intervention with proper supportive care will enhance patients' quality of life, ultimately affecting patients' compliance.