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Treatment Patterns and Clinical Outcomes Among Patients With ROS1-rearranged Non–small-cell Lung Cancer Progressing on Crizotinib

2020; Elsevier BV; Volume: 21; Issue: 5 Linguagem: Inglês

10.1016/j.cllc.2020.03.008

1938-0690

Andrea De Giglio, Giuseppe Lamberti, Francesco Facchinetti, Carlo Genova, Elisa Andrini, Maria Giovanna Dal Bello, Marcello Tiseo, Giulio Metro, Rita Chiari, Biagio Ricciuti,

Colorectal Cancer Treatments and Studies

Background ROS1 rearrangements define a subset of non–small-cell lung cancers (NSCLCs) that are susceptible to therapeutic ROS1 kinase inhibition. Despite the fact that most patients initially respond to the first-generation ROS1 tyrosine kinase inhibitor (TKI) crizotinib, relapse invariably occurs, and therapeutic options upon disease progression are limited. Patients and Methods We conducted a multicenter study of patients with ROS1-rearranged NSCLC who progressed on ROS1 TKIs and examined the clinical outcomes based on the post-progression treatment approaches. Results Among 29 patients with ROS1-rearrangement who received at least 1 ROS1 inhibitor, the median age was 51 years (range, 30-80 years), 70.8% of patients were female, and 68.9% were never-smokers. Upon progression to the first TKI, 11 patients (37.9%) received treatment with TKIs beyond progression. The median second progression-free survival to TKIs in patents treated beyond progression was 5.5 months (95% confidence interval [CI], 4.1-9.1 months), whereas the post-progression survival was 21.0 months (95% CI, 5.5 months-not reached [NR]). Eleven (37.9%) patients received a sequential treatment with lorlatinib ROS1 TKIs following a first generation ROS1 TKI. The overall response rate, median progression-free survival, and median overall survival (OS) to next-generation TKIs were 41.7% (95% CI, 15.2%-72.3%), 12.7 months (95% CI, 8.5 months-NR), and 17.0 months (95% CI, 15.8 months-NR), respectively. Patients treated with sequential ROS1 TKIs had a significantly longer median OS compared with those who were not (NR vs. 16.1 months; hazard ratio, 0.26; 95% CI, 0.10-0.78; P = .017). Conclusion In this study, we reported that a subset of patients with ROS1-rearranged NSCLC may benefit from treatment with TKIs beyond progression and that sequential treatment with crizotinib followed by lorlatinib is associated with improved OS in patients with ROS1-rearranged NSCLC.