Brief Report: Final overall survival and long-term safety of lorlatinib in patients with ALK-positive non-small cell lung cancer from the pivotal phase 2 study

Abstract

IntroductionLorlatinib is a potent, brain-penetrant, third-generation inhibitor of anaplastic lymphoma kinase (ALK) and ROS1 tyrosine kinases with broad coverage of ALK resistance mutations. We present overall survival (OS) and long-term safety of lorlatinib in patients with advanced ALK-positive non-small cell lung cancer (NSCLC) from the final analyses of the pivotal phase 2 study. MethodsAdults with ALK-positive NSCLC, enrolled in expansion cohorts based on prior therapy (EXP1-5), received lorlatinib 100 mg orally once daily in continuous 21-day cycles. The primary endpoint was objective response rate; secondary endpoints included OS and safety. ResultsThirty patients were enrolled in EXP1 (treatment naïve), 59 in EXP2-3A (disease progression following crizotinib ± chemotherapy), 28 in EXP3B (disease progression following one second-generation ALK tyrosine kinase inhibitor [TKI] ± chemotherapy), 111 in EXP4-5 (disease progression following ≥2 ALK TKIs ± chemotherapy), and 139 in EXP3B-5 (disease progression following ≥1 ALK TKI ± chemotherapy). Median OS was not reached (NR) (95% CI, NR-NR) in EXP1, NR (95% CI, 51.5-NR) in EXP2-3A, 37.4 months (95% CI, 12.3-NR) in EXP3B, 19.2 months (95% CI, 15.4-30.2) in EXP4-5, and 20.7 months (95% CI, 16.1-30.3) in EXP3B-5. All-cause adverse events leading to dose reduction were reported in 77 (28%) patients, temporary treatment discontinuation in 158 (57%), and permanent discontinuation in 35 (13%). ConclusionsAfter a minimum follow-up of 5 years, final analyses from the global phase 2 study confirmed substantial activity, prolonged OS, and generally consistent safety findings with lorlatinib in treatment-naïve and previously treated patients with ALK-positive NSCLC.