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Research Article|Articles in Press, 100499

Asian Subgroup Analysis of the Randomized Phase 3 CROWN Study of First-Line Lorlatinib vs Crizotinib in Advanced ALK-Positive Non-Small Cell Lung Cancer

Open AccessPublished:March 10, 2023DOI:https://doi.org/10.1016/j.jtocrr.2023.100499
Asian Subgroup Analysis of the Randomized Phase 3 CROWN Study of First-Line Lorlatinib vs Crizotinib in Advanced ALK-Positive Non-Small Cell Lung Cancer
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      Abstract

      Introduction

      Lorlatinib is a potent, third-generation inhibitor of anaplastic lymphoma kinase (ALK). In the planned interim analysis of the ongoing, Phase 3, randomized, global CROWN trial (NCT03052608), lorlatinib resulted in significantly longer progression-free survival (PFS) than crizotinib in patients with previously untreated, advanced, ALK-positive non-small cell lung cancer. Here, we present a subgroup analysis of Asian patients in the CROWN study.

      Methods

      Patients received lorlatinib 100 mg once daily or crizotinib 250 mg twice daily. The primary endpoint was PFS assessed by blinded independent central review (BICR). Objective response rate (ORR), intracranial ORR, safety, and select biomarkers were secondary endpoints.

      Results

      At data cutoff (September 20, 2021), 120 patients were included in the Asian intention-to-treat subgroup (lorlatinib n=59; crizotinib n=61). At 36 months, 61% (95% confidence interval [CI], 47–72) and 25% (95% CI, 12–41) of patients in the lorlatinib and crizotinib groups, respectively, were alive without disease progression (hazard ratio for disease progression by BICR or death: 0.40; 95% CI, 0.23–0.71). ORR was 78% (95% CI, 65–88) vs 57% (95% CI, 44–70) for patients treated with lorlatinib and crizotinib, respectively. In patients with measurable and/or non-measurable brain metastases at baseline, intracranial ORR was 73% (95% CI, 39–94) vs 20% (95% CI, 4–48) for patients treated with lorlatinib and crizotinib, respectively. Hypercholesterolemia, hypertriglyceridemia, and edema were the most commonly reported adverse events with lorlatinib.

      Conclusions

      Lorlatinib efficacy and safety in the Asian subgroup of CROWN were consistent with those in the overall population.

      Keywords

      Article info

      Publication history

      Accepted: March 5, 2023
      Received: January 17, 2023

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      Disclosure of funding

      This study was sponsored by Pfizer Inc.

      Declaration of interest

      Y-LW reports advisory services for AstraZeneca, Boehringer Ingelheim, Novartis, and Takeda; personal fees from AstraZeneca, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, MSD, Pfizer, Roche, and Sanofi; and grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Hengrui, and Roche, outside the submitted work. QZ reports honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, MSD, Pfizer, Roche, and Sanofi, outside the submitted work. RAS reports consulting for AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Pfizer, Roche/Genentech, Taiho Pharmaceutical, Yuhan, Takeda, Amgen, Lilly, and Merck; honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Novartis, Pfizer, Roche/Genentech, Takeda, Yuhan, Amgen, Bayer, and Merck; and research funding from AstraZeneca and Boehringer Ingelheim. C-HC reports honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharma, Lilly, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche, and Takeda and consulting for Lilly, MSD, Novartis, and Roche. HH reports research grants from AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., and Ono Pharmaceutical Co. Ltd. ST reports honoraria from Chugai Pharma, Novartis, AstraZeneca, Taiho Pharmaceutical, Ono Pharmaceutical, and Boehringer Ingelheim. YG reports grant support, lecture fees, and advisory board fees from Lilly, Taiho Pharmaceutical, Pfizer, Novartis, MSD, Ono Pharmaceutical, Kyorin Pharmaceutical, and Bristol Myers Squibb; lecture fees and advisory board fees from Chugai Pharmaceutical, Boehringer Ingelheim, and AstraZeneca; grant support and advisory board fees from Guardant Health and Daiichi Sankyo; and advisory board fees from Illumina. VH-FL reports honoraria from Roche, Pfizer, AstraZeneca, Takeda, Novartis, MSD, Lilly, and Amgen and research support grants from AstraZeneca, Pfizer, and Varian Medical Systems. D-WK reports travel support for advisory board meeting attendance from Daiichi Sankyo and Amgen and research funding to affiliated institution from Alpha Biopharma, Amgen, AstraZeneca/MedImmune, Boehringer Ingelheim, Daiichi Sankyo, Hanmi, Janssen, Pfizer, SK Biopharmaceuticals, Takeda, and Yuhan. JCMH reports honoraria from AstraZeneca, Roche, Pfizer, Boehringer Ingelheim, MSD, Lilly, Bristol Myers Squibb, Novartis, and Takeda and grants from Roche and AstraZeneca. C-CL reports honoraria from Lilly, Novartis, and Roche; consulting for AbbVie, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Lilly, Merck KGaA, Novartis, and PharmaEngine; and travel grants from BeiGene and Lilly. SL reports grants from AstraZeneca, Hutchison MediPharma, Bristol Myers Squibb, Heng Rui, and Roche; speakers’ fees from AstraZeneca, Roche, and Hansoh Pharma; and consultant fees from AstraZeneca, Boehringer Ingelheim, Hutchison MediPharma, Simcere, ZaiLab, GenomiCare, and Roche. AP, AMC, J-FM, and CHW are employees of Pfizer Inc and may own stock or stock options in Pfizer. TM reports research funding from AstraZeneca, Bristol Myers Squibb, Clovis Oncology, G1 Therapeutics, MSD, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, and Xcovery; speaker fees from ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before January 2019), Boehringer Ingelheim, Bristol Myers Squibb, Lilly, InMed Medical Communication, MSD, Novartis, Pfizer, prIME Oncology, Roche/Genentech, and Taiho; honoraria from AbbVie, Inc., ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca, Bayer, Boehringer Ingelheim, Blueprint Medicines Corporation, Bristol Myers Squibb, Celgene, CStone Pharmaceuticals, Daiichi Sankyo, Lilly, and Fishawack; shares in Hutchison Chi-Med and Sanomics Ltd.; and advisory board service for AbbVie, Inc., ACEA Pharma, Amgen, AstraZeneca, Bayer, Blueprint Medicine Corporation, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cirina, CStone Pharmaceuticals, Daiichi Sankyo, Lilly, Fishawack Facilitate, Ltd., G1 Therapeutics, Inc., and GeneDx. HRK reports advisory services for AstraZeneca, MSD, and grants from AstraZeneca, Bristol Myers Squibb, Ono, and Roche, outside the submitted work.

      G-CC, S-WK, JZ, and BH have nothing to report.

      Abbreviations: AE, adverse event; ALK, anaplastic lymphoma kinase; BICR, blinded independent central review; CI, confidence interval; CNS, central nervous system; ctDNA, circulating tumor DNA; DOR, duration of response; HR, hazard ratio; NR, not reached; NSCLC, non-small cell lung cancer; ORR, objective response rate; PFS, progression-free survival; PK, pharmacokinetics; RECIST, Response Evaluation Criteria in Solid Tumors; TEAE, treatment-emergent adverse event; TKI, tyrosine kinase inhibitor.

      Author contribution statement

      Yi-Long Wu: Data curation, Methodology, Investigation, Formal Analysis, Writing - Original Draft, Writing - Review & Editing. Qing Zhou: Data curation, Investigation, Formal Analysis, Writing - Original Draft, Writing - Review & Editing. Ross A. Soo: Data curation, Investigation, Writing - Original Draft, Writing - Review & Editing. Gee-Chen Chang: Data curation, Investigation, Writing - Original Draft, Writing - Review & Editing. Chao-Hua Chiu: Data curation, Investigation, Writing - Original Draft, Writing - Review & Editing. Hidetoshi Hayashi: Data curation, Investigation, Writing - Original Draft, Writing - Review & Editing. Sang-We Kim: Data curation, Investigation, Writing - Original Draft, Writing - Review & Editing. Shunsuke Teraoka: Data curation, Investigation, Writing - Original Draft, Writing - Review & Editing. Yasushi Goto: Data curation, Methodology, Investigation, Formal Analysis, Writing - Original Draft, Writing - Review & Editing. Jianying Zhou: Data curation, Investigation, Writing - Original Draft, Writing - Review & Editing. Victor Ho-Fun Lee: Data curation, Investigation, Writing – Original Draft, Writing – Review & Editing. Dong-Wan Kim: Data curation, Investigation, Writing - Original Draft, Writing - Review & Editing. Baohui Han: Data curation, Investigation, Writing – Original Draft, Writing – Review & Editing. James Chung Man Ho: Data curation, Investigation, Writing - Original Draft, Writing - Review & Editing Chia-Chi Lin: Data curation, Investigation, Writing - Original Draft, Writing - Review & Editing. Shun Lu: Data curation, Investigation, Writing - Original Draft, Writing - Review & Editing. Anna Polli: Data curation, Methodology, Investigation, Formal Analysis, Writing - Original Draft, Writing - Review & Editing.

      Anna Maria Calella: Formal Analysis, Writing - Original Draft, Writing - Review & Editing Jean-François Martini: Data curation, Methodology, Investigation, Formal Analysis, Writing – Original Draft, Writing – Review & Editing. Chew Hooi Wong: Formal Analysis, Writing - Original draft, Writing – Review & Editing Tony Mok: Data curation, Investigation, Writing - Original Draft, Writing - Review & Editing. Hye Ryun Kim: Data curation, Investigation, Formal Analysis, Writing - Original Draft, Writing - Review & Editing.

      All authors critically reviewed the manuscript and approved the final version for submission.

      Identification

      DOI: https://doi.org/10.1016/j.jtocrr.2023.100499

      Copyright

      © 2023 Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.

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