Efficacy of Immune Checkpoint Inhibitor Monotherapy for Advanced Non-Small-Cell Lung Cancer with ALK Rearrangement

概要

Programmed death-ligand 1 (PD-L1) expression is a predictor of immune checkpoint inhibitor (ICI) treatment efficacy. The clinical efficacy of PD-1 inhibitors for NSCLC patients harboring major mutations, such as EGFR or ALK, is limited. ALK gene rearrangement occurs in a small portion of patients with non-small cell lung cancer (NSCLC), but it accounts for about 30–40% of lung adenocarcinoma in young people and is present in many non-smokers. It has been reported that programmed death-ligand 1 (PD-L1) expression is high in ALK-positive lung cancer. PD-L1 expression is one of the predictors of efficacy for ICI treatment. However, there are few reports of studies that have investigated the efficacy of PD-1 inhibitors in ALK-rearranged NSCLC patients. Therefore, we compared the efficacies of ICIs for treatment of ALK-positive lung adenocarcinoma and other oncogene drivers, including EGFR mutations. We genotyped 190 advanced lung adenocarcinomas who received nivolumab or pembrolizumab monotherapy and examined the efficacy in NSCLC patients with or without major mutations. Forty-seven patients harbored the EGFR mutation, 25 had KRAS, 5 had a HER2, 6 had a BRAF, and 7 had ALK rearrangement. The status of PD-L1 expression was evaluated in 151 patients, and the rate of high PD-L1 expression (≥50%) was significantly higher in patients with ALK mutations. The progression-free survival was 0.6 (95% CI:0.2-2.1) months for ALK-positive patients and 1.8 (95% CI:1.2-2.1) months for EGFR-positive patients. All patients with ALK rearrangement showed disease progression within 3 months from the initiation of anti-PD-1 treatment. Our data suggested that ICI treatment was significantly less efficacious in patients with ALK rearrangement than in patients with EGFR mutations, and PD-L1 expression is not a critical biomarker for ICI treatment for patients with either mutations.