Viola W Zhu1, Yen-Ting Lin2, Dong-Wan Kim3, Herbert H Loong4, Misako Nagasaka5, Hao To6, Yvonne Li-En Ang7, Chan-Young Ock3, Nishan Tchekmedyian8, Sai-Hong Ignatius Ou9, Nicholas L Syn10, Thanyanan Reungwetwattana11, Chia-Chi Lin2, Ross A Soo7. 1. Chao Family Comprehensive Cancer Center, University of California, Irvine School of Medicine, Orange, California. 2. Department of Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University Cancer Center, National Taiwan University, Taipei, Taiwan, Republic of China; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China. 3. Department of Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. 4. Department of Clinical Oncology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People's Republic of China. 5. Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan. 6. University of Nevada School of Medicine, Reno, Nevada. 7. Department of Hematology-Oncology, National University Cancer Institute, Singapore. 8. Pacific Shores Medical Group, Long Beach, California. 9. Chao Family Comprehensive Cancer Center, University of California, Irvine School of Medicine, Orange, California. Electronic address: siou@hs.uci.edu. 10. Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 11. Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Abstract
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.
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.
Authors: Maximilian J Hochmair; Hannah Fabikan; Oliver Illini; Christoph Weinlinger; Ulrike Setinek; Dagmar Krenbek; Helmut Prosch; Markus Rauter; Michael Schumacher; Ewald Wöll; Romana Wass; Elmar Brehm; Gudrun Absenger; Tatjana Bundalo; Peter Errhalt; Matthias Urban; Arschang Valipour Journal: Pharmaceuticals (Basel) Date: 2020-11-07
Authors: Francesco Facchinetti; Antonin Levy; Samy Ammari; Charles Naltet; Pernelle Lavaud; Mihaela Aldea; Damien Vasseur; David Planchard; Benjamin Besse Journal: Cancer Manag Res Date: 2021-03-26 Impact factor: 3.989
Authors: Smitha Mellacheruvu; Mark N Sayegh; R Alejandro Sica; Haiying Cheng; Maria Laureana Santos-Zabala; Jacob H Gebrael; Ulrich Hermanto; Norman L Rosen Journal: JCO Precis Oncol Date: 2022-02
Authors: Sergey V Orlov; Aglaya G Iyevleva; Elena A Filippova; Alexandra M Lozhkina; Svetlana V Odintsova; Tatiana N Sokolova; Natalia V Mitiushkina; Vladislav I Tiurin; Elena V Preobrazhenskaya; Alexandr A Romanko; Alexandr S Martianov; Alexandr O Ivantsov; Svetlana N Aleksakhina; Alexandr V Togo; Evgeny N Imyanitov Journal: Transl Oncol Date: 2021-05-21 Impact factor: 4.243
Authors: Nikolaj Frost; Petros Christopoulos; Diego Kauffmann-Guerrero; Jan Stratmann; Richard Riedel; Monica Schaefer; Jürgen Alt; Sylvia Gütz; Daniel C Christoph; Eckart Laack; Martin Faehling; Richard Fischer; Klaus Fenchel; Sebastian Haen; Lukas Heukamp; Christian Schulz; Frank Griesinger Journal: Ther Adv Med Oncol Date: 2021-02-09 Impact factor: 8.168