PMID- 35660971 OWN - NLM STAT- MEDLINE DCOM- 20220621 LR - 20221207 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 169 DP - 2022 Jul TI - Efficacy and safety of lorlatinib in Asian and non-Asian patients with ALK-positive advanced non-small cell lung cancer: Subgroup analysis of a global phase 2 trial. PG - 67-76 LID - S0169-5002(22)00453-6 [pii] LID - 10.1016/j.lungcan.2022.05.012 [doi] AB - OBJECTIVES: To analyze the efficacy and safety of lorlatinib in Asian and non-Asian patients with pretreated anaplastic lymphoma kinase (ALK)-positive, advanced non-small cell lung cancer (NSCLC) from a phase 1/2 study. MATERIALS AND METHODS: In this ongoing phase 2 part of the trial, patients with ALK- or ROS1-positive, advanced NSCLC enrolled into six expansion cohorts (EXP1-6), based on ALK and ROS1 status and previous therapy, and received lorlatinib 100 mg once daily. The primary endpoint was objective tumor response and intracranial response. Post hoc analyses of activity were conducted in Asian and non-Asian (based on race) ALK-positive patients who received either previous crizotinib with or without chemotherapy (EXP2-3A) or at least one second-generation ALK tyrosine kinase inhibitor with any number of chemotherapy regimens (EXP3B-5). Analysis of safety (adverse events [AEs]) was in the phase 1 and 2 study population who started lorlatinib 100 mg once daily. RESULTS: 17 Asian patients were enrolled in EXP2-3A and 53 in EXP3B-5; 33 non-Asian patients were enrolled in EXP2-3A and 73 in EXP3B-5. Objective response rates in the Asian and non-Asian subgroups were 82.4% (95% confidence interval [CI]: 56.6-96.2) and 63.6% (95% CI: 45.1-79.6) in EXP2-3A, and 47.2% (95% CI: 33.3-61.4) and 30.1% (95% CI: 19.9-42.0) in EXP3B-5, and median progression-free survival was 13.6 and 12.5 months (EXP2-3A) and 6.9 and 5.5 months (EXP3B-5). Lorlatinib exhibited antitumor activity across ALK resistance mutations, while no differences according to the EML4-ALK variant could be detected. The most common treatment-related AEs were hypercholesterolemia, hypertriglyceridemia, edema, and peripheral neuropathy in both Asian and non-Asian subgroups. CONCLUSION: Lorlatinib showed substantial overall and intracranial activity in pretreated patients with ALK-positive NSCLC in both Asian and non-Asian patients. AE profiles were similar between Asian and non-Asian patients. CLINICALTRIALS: gov NCT01970865. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Soo, Ross A AU - Soo RA AD - National University Hospital, Singapore. Electronic address: ross_soo@nuhs.edu.sg. FAU - Huat Tan, Eng AU - Huat Tan E AD - National Cancer Centre, Singapore. Electronic address: tan.eng.huat@singhealth.com.sg. FAU - Hayashi, Hidetoshi AU - Hayashi H AD - Kindai University, Faculty of Medicine, Osaka-Sayama, Japan. Electronic address: hidet31@med.kindai.ac.jp. FAU - Seto, Takashi AU - Seto T AD - National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. FAU - Lin, Chia-Chi AU - Lin CC AD - National Taiwan University Hospital, Taipei, Taiwan. Electronic address: cclin1@ntu.edu.tw. FAU - Ou, Sai-Hong Ignatius AU - Ou SI AD - Chao Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA, USA. Electronic address: siou@uci.edu. FAU - Kim, Dong-Wan AU - Kim DW AD - Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: kimdw@snu.ac.kr. FAU - Liu, Geoffrey AU - Liu G AD - Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. Electronic address: geoffrey.liu@uhn.ca. FAU - Abbattista, Antonello AU - Abbattista A AD - Pfizer Oncology, Milan, Italy. Electronic address: antonello.abbattista@pfizer.com. FAU - Martini, Jean-Francois AU - Martini JF AD - Pfizer Oncology, La Jolla, CA, USA. Electronic address: jean-francois.martini@pfizer.com. FAU - Hooi Wong, Chew AU - Hooi Wong C AD - Pfizer Pte Ltd, Singapore. Electronic address: chewhooi.wong@pfizer.com. FAU - Toffalorio, Francesca AU - Toffalorio F AD - Pfizer Oncology, Milan, Italy. Electronic address: francesca.toffalorio@pfizer.com. FAU - Solomon, Benjamin J AU - Solomon BJ AD - Peter MacCallum Cancer Centre, Melbourne, Australia. Electronic address: Ben.Solomon@petermac.org. LA - eng SI - ClinicalTrials.gov/NCT01970865 PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220523 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Aminopyridines) RN - 0 (Lactams) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Pyrazoles) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - OSP71S83EU (lorlatinib) SB - IM MH - Aminopyridines/adverse effects MH - Asian People/genetics/statistics & numerical data MH - *Carcinoma, Non-Small-Cell Lung/drug therapy/ethnology/genetics/pathology MH - Humans MH - Lactams/adverse effects MH - *Lung Neoplasms/drug therapy/ethnology/genetics/pathology MH - Protein Kinase Inhibitors/adverse effects MH - Protein-Tyrosine Kinases/genetics MH - Proto-Oncogene Proteins/genetics MH - Pyrazoles/adverse effects OTO - NOTNLM OT - Anaplastic lymphoma kinase OT - Asian OT - Lorlatinib OT - Non-small cell lung cancer OT - Tyrosine kinase inhibitor EDAT- 2022/06/07 06:00 MHDA- 2022/06/22 06:00 CRDT- 2022/06/06 12:01 PHST- 2022/01/24 00:00 [received] PHST- 2022/05/06 00:00 [revised] PHST- 2022/05/22 00:00 [accepted] PHST- 2022/06/07 06:00 [pubmed] PHST- 2022/06/22 06:00 [medline] PHST- 2022/06/06 12:01 [entrez] AID - S0169-5002(22)00453-6 [pii] AID - 10.1016/j.lungcan.2022.05.012 [doi] PST - ppublish SO - Lung Cancer. 2022 Jul;169:67-76. doi: 10.1016/j.lungcan.2022.05.012. Epub 2022 May 23.