Background

Lorlatinib improved progression-free survival (PFS) and demonstrated intracranial (IC) activity in patients with untreated advanced ALK+ non-small cell lung cancer (NSCLC) in the phase III CROWN study (NCT03052608) of lorlatinib vs crizotinib. Here, we report updated results in the Asian subgroup from this study after 36 months of follow-up.

Methods

Patients were randomized 1:1 to receive lorlatinib 100 mg once daily or crizotinib 250 mg twice daily, stratified by presence of brain metastases (yes/no) and ethnicity (Asian/non-Asian). The primary endpoint was PFS by based on blinded independent central review (BICR). Key secondary endpoints included objective response rate (ORR), intracranial ORR (IC ORR), IC time to progression (IC TTP), and safety. Endpoints were analyzed using unstratified analyses in the Asian subgroup.

Results

In the Asian subgroup, 120 patients were randomized to lorlatinib (n=59) or crizotinib (n=61) arm. At data cutoff (Sep 20, 2021), median PFS by BICR was not reached with lorlatinib and 11.1 months with crizotinib (HR 0.40; 95% CI, 0.230-0.710; Table). Both ORR and IC ORR were clinically improved with lorlatinib vs crizotinib. The HR of IC TTP with lorlatinib vs crizotinib was 0.03 (95% CI, 0.004-0.200). All-cause grade 3/4 treatment-emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were reported in 79.7% and 8.5% of patients with lorlatinib and 61.7% and 13.3% of patients with crizotinib, respectively. No new safety signals emerged. Table: 992P

Efficacy in CROWN Asian subgroup ^a

Conclusions

Efficacy and safety results in the Asian subgroup were consistent with those in the overall population in the CROWN study. Our data support the use of lorlatinib as a first-line treatment option in Asian patients with ALK+ NSCLC.

Clinical trial identification

NCT03052608.

Editorial acknowledgement

Editorial and medical writing support was provided by Ravi Subramanian of ClinicalThinking and was funded by Pfizer.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

Z. Qing: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, Sanofi. R.A. Soo: Financial Interests, Personal, Advisory Board: Amgen, Astra-Zeneca, Bayer, BMS, Lily, Merck, Novartis, Pfizer, Roche, Takeda, Yuhan; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Other, Conference sponsorship: Taiho; Financial Interests, Institutional, Research Grant: Astra-Zeneca, Boehringer Ingelheim. C.H. Chiu: Non-Financial Interests, Personal, Invited Speaker: Taipei Veterans General Hospital; Non-Financial Interests, Personal, Advisory Board: Taipei Veterans General Hospital; Non-Financial Interests, Personal, Principal Investigator: Taipei Veterans General Hospital. H. Hayashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Bristol Myers Squibb Co. Ltd, AstraZeneca K.K, Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K, Merck Biopharma Co. Ltd, MSD K.K., Novartis Pharmaceuticals K.K, Pfizer, Takeda Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K.; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb Co. Ltd, Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K, Shanghai Haihe Biopharm, Pfizer, AstraZeneca K.K; Financial Interests, Institutional, Funding: AstraZeneca K.K., Astellas Pharma Inc., MSD K.K., Ono Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., grants, Pfizer Japan Inc., Bristol Myers Squibb Company, Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Daiichi; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., and Ono Pharmaceutical Co. Ltd.; Non-Financial Interests, Principal Investigator: Ono Pharmaceutical Co. Ltd. and Bristol Myers Squibb Co; Non-Financial Interests, Member: West Japan Oncology Group, Japan Society of Medical Oncology. S. Teraoka: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Advisory Board: Pfizer R&D Japan G.K. D. Kim: Financial Interests, Invited Speaker: Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology, Taiwan Lung Cancer Society, Asian Thoracic Oncology Research Group; Other, Writing Engagements: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Chong Keun Dang, Daiichi Sankyo, GSK, Pfizer, MSD, Merck, Novartis, Roche, Takeda, Yuhan; Non-Financial Interests, Advisory Board: Amgen, AstraZeneca, BMS/Ono Pharmaceuticals, Daiichi Sankyo, GSK, Janssen, Merck, MSD, Pfizer, SK Biopharm, Takeda; Other, Member of the Board of Directors: Asian Thoracic Oncology Research Group, Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology; Financial Interests, Institutional, Research Grant: Alpha Biopharma, Amgen, AstraZeneca/MedImmune, Boehringer Ingelheim, BMS, Bridge BioTherapeutics, Chong Keun Dang, Daiichi Sankyo, GSK, Hanmi, Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan; Other, Principal Investigator: Chong Keun Dang; Financial Interests, Advisory Role: Scientific advisor for Health insurance review and assessment service, Korea; Other, Travel Support: Amgen, Daiichi Sankyo, International Association for the Study of Lung Cancer, Asian Thoracic Oncology Research Group, Taiwan Lung Cancer Society. H. Zhan: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc. H. Zhao: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc. H. Li: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc. T.S.K. Mok: Financial Interests, Personal, Invited Speaker: AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Fishawack Facilitate, InMed Medical Communication, Lunit USA, Inc., Merck Serono, MSD, Roche, MD Health, Medscape/WebMD, PeerVoice, Permanyer SL, Prime Oncology, Research to Practice, Touch Medical Media, Sanofi-Aventis, Takeda, PER, AstraZeneca, Hutchison Chi-Med; Financial Interests, Personal, Advisory Board: AbbVie, Acea Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Blueprint Medicines, Berry Oncology, CStone Pharma, Daiichi Sankyo, Fishawack Facilitate, Eisai, Gritstone Oncology, Guardant Health, G1 Therapeutics, Hengrui, Ignyta, IQVIA, Incyte Corporation, Inivata, Janssen, Loxo Oncology, Qiming Dev., Lunit USA, Inc., Merck Serono, MSD, Roche, Mirati Therapeutics, MoreHealth, Novartis, OrigiMed, Puma Tech., Sanofi-Aventis, Takeda, Virtus Medical, Yuhan, Curio Science; Financial Interests, Personal, Stocks/Shares: Sanomics Ltd., Hutchison Chi-Med, Biolidics Ltd., Loxo Oncology, OrigiMed Co., Virtus Medical Group, Lunit USA, Inc., Aurora Tele-Oncology; Financial Interests, Institutional, Funding, For clinical trials performed at CUHK: AstraZeneca, BMS, Merck Serono, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery, Takeda, G1 Therapeutics, Clovis Oncology; Non-Financial Interests, Advisory Role: geneDecode, AstraZeneca; Non-Financial Interests, Other, Invited Speaker: AstraZeneca; Non-Financial Interests, Invited Speaker: Aurora Tele-Oncology, Lunit USA, Inc., Sanomics Ltd.; Non-Financial Interests, Leadership Role: American Society of Clinical Oncology (ASCO), Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Chinese Society of Clinical Oncology (CSCO), Hong Kong Cancer Fund (HKCF), Hong Kong Cancer Therapy Society (HKCTS), St. Stephen’s College & Prep. School (Hong Kong); Non-Financial Interests, Leadership Role, Term ended on 30 April 2019: International Association for the Study of Lung Cancer (IASLC). Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda; Financial Interests, Invited Speaker: AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, Yunhan, Eli Lilly; Non-Financial Interests, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non-Financial Interests, Other, WCLC 2020 Conference Chair: IASLC; Non-Financial Interests, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO). All other authors have declared no conflicts of interest.