An International Real-World Analysis of the Efficacy and Safety of Lorlatinib Through Early or Expanded Access Programs in Patients With Tyrosine Kinase Inhibitor–Refractory ALK-Positive or ROS1-Positive NSCLC

Lorlatinib, a next-generation central nervous system–penetrant ALK/ROS1 tyrosine kinase inhibitor (TKI), is approved to treat TKI-refractory ALK-positive (ALK+) NSCLC based on results from a phase 2 study. A real-world analysis was performed on ALK+ or ROS1-positive (ROS1+) patients with NSCLC enrolled in lorlatinib early or expanded access programs in Hong Kong, Singapore, South Korea, Taiwan, Thailand, and the United States. A total of 95 patients with NSCLC (76 ALK+ and 19 ROS1+) were analyzed. Among ALK+ patients treated with less than two previous TKIs, two or more previous TKIs, and three or more previous TKIs, the objective response rates (ORR) and median progression-free survival (mPFS) were 42% (95% confidence interval [CI]: 26–59; n = 38) and not reached (NR) (95% CI: 4.5–NR; n = 45), 35% (95% CI: 22–49; n = 55) and 11.2 months (95% CI: 4.5–NR; n = 66), and 18% (95% CI: 4–43; n = 17) and 6.5 months (95% CI: 3.5–11.6; n = 21), respectively. The ORRs and mPFSs were 13% (95% CI: 0–53; n = 8) and 9.2 months (95% CI: 3.3–NR; n = 9) for patients treated with one second-generation ALK TKI as the only ALK TKI received. For ROS1+ patients, ORRs and mPFSs were 41% (95% CI: 18–67; n = 17) and 11.9 months (95% CI: 6.4–NR; n = 19). The intracranial ORRs were 35% (95% CI: 22–49) and 55% (95% CI: 23–83) for 52 ALK+ and 11 ROS1+ patients. mPFS was 9.3 months (95% CI: 1.0–NR; n = 13) for patients with leptomeningeal carcinomatosis. No new safety signals were noted. Lorlatinib exhibited meaningful activity in TKI-refractory ALK+ or ROS1+ patients with NSCLC enrolled in early or expanded access programs.