Viola W. ZhuYen Ting LinDong Wan KimHerbert H. LoongMisako NagasakaHao ToYvonne Li En AngChan Young OckNishan TchekmedyianSai Hong Ignatius OuNicholas L. SynThanyanan ReungwetwattanaChia Chi LinRoss A. SooNational Taiwan University HospitalYong Loo Lin School of MedicineNational Taiwan University College of MedicineSeoul National University HospitalWayne State University School of MedicineNational University of SingaporeFaculty of Medicine, Ramathibodi Hospital, Mahidol UniversityUCI School of MedicineUniversity of Nevada School of MedicineChinese University of Hong KongPacific Shores Medical Group2020-08-252020-08-252020-01-01Journal of Thoracic Oncology. (2020)15561380155608642-s2.0-85086020844https://repository.li.mahidol.ac.th/handle/20.500.14594/58338© 2020 International Association for the Study of Lung Cancer Introduction: 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. Methods: 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. Results: 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. Conclusion: Lorlatinib exhibited meaningful activity in TKI-refractory ALK+ or ROS1+ patients with NSCLC enrolled in early or expanded access programs.Mahidol UniversityMedicineArticleSCOPUS10.1016/j.jtho.2020.04.019