Entrectinib for ROS1-rearranged non-small cell lung cancer after crizotinib-induced interstitial lung disease: A case report

Chromosomal rearrangements involving the c-ros oncogene 1 (ROS1) are identified in approximately 1% of non-small cell lung cancer (NSCLC) patients. Crizotinib is the first tyrosine kinase inhibitor (TKI) against ROS1-rearranged NSCLC. G2032R, a secondary resistant mutation, is observed in 41% of patients treated with crizotinib. Entrectinib, a TKI against neurotrophic tropomyosin receptor kinase, is reportedly efficacious against ROS1-rearranged NSCLC. However, ROS1-G2032R is resistant to entrectinib both in vitro and in vivo. We report an 85-year-old female patient with ROS1-rearranged NSCLC, who developed drug-induced interstitial lung disease (DI-ILD) 2 months after crizotinib treatment, and was treated with prednisolone followed by entrectinib. Entrectinib treatment resulted in stable disease with a marginal response after a partial response to crizotinib. Entrectinib treatment following crizotinib cessation due to DI-ILD was efficacious, which suggested that ROS1-G2032R gatekeeper mutation, frequently observed in crizotinib-resistant disease, was absent.