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Research Article|Articles in Press, 100471

First-line lorlatinib versus crizotinib in ALK-positive non-small cell lung cancer: Japanese subgroup analysis of CROWN

  • Hidetoshi Hayashi
    Correspondence
    Corresponding author: Hidetoshi Hayashi, MD, PhD, Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan, Telephone: +81-72-366-0221, Fax: +81-72-360-5000.
    Affiliations
    Kindai University Faculty of Medicine, 377-2 Onohigashi, Osakasayama, Osaka, 589-8511, Japan
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  • Shunsuke Teraoka
    Affiliations
    Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8509, Japan
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  • Yasushi Goto
    Affiliations
    National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
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  • Toru Kumagai
    Affiliations
    Osaka International Cancer Institute, 3 Chome-1-69 Otemae, Chuo Ward, Osaka, 541-8567, Japan
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  • Makoto Nishio
    Affiliations
    The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
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  • Shunichi Sugawara
    Affiliations
    Sendai Kousei Hospital, 980-0873 Miyagi, Aoba Ward, Hirosemachi, Sendai, 4−15 2, Japan
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  • Satoshi Oizumi
    Affiliations
    National Hospital Organization Hokkaido Cancer Center, 2 Chome-3-54 Kikusui 4 Jo, Shiroishi Ward, Sapporo, Hokkaido, 003-0804, Japan
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  • Masakazu Matsumura
    Affiliations
    Pfizer R&D Japan, 3-22-7 Yoyogi, Shibuya-ku, Tokyo, 151-8589, Japan
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  • Author Footnotes
    ∗ Masayuki Okura is a former Pfizer employee and was involved in the design of the study, data analysis, and drafting and revising the manuscript.
    Masayuki Okura
    Footnotes
    ∗ Masayuki Okura is a former Pfizer employee and was involved in the design of the study, data analysis, and drafting and revising the manuscript.
    Affiliations
    Formerly of Pfizer R&D Japan; * 3-22-7 Yoyogi, Shibuya-ku, Tokyo, 151-8589, Japan
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  • Author Footnotes
    † Gerson Peltz is a former Pfizer employee and was involved in the design of the study, and drafting and revising the manuscript.
    Gerson Peltz
    Footnotes
    † Gerson Peltz is a former Pfizer employee and was involved in the design of the study, and drafting and revising the manuscript.
    Affiliations
    Formerly of Pfizer Oncology, †280 Shennecossett Rd, Groton, CT 06340 , USA
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  • Terufumi Kato
    Affiliations
    Kanagawa Cancer Center, Nakao 2-3-2, Asahi-ku, Yokohama, 241-8515, Japan
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  • Author Footnotes
    ∗ Masayuki Okura is a former Pfizer employee and was involved in the design of the study, data analysis, and drafting and revising the manuscript.
    † Gerson Peltz is a former Pfizer employee and was involved in the design of the study, and drafting and revising the manuscript.
Open AccessPublished:February 02, 2023DOI:https://doi.org/10.1016/j.jtocrr.2023.100471
First-line lorlatinib versus crizotinib in ALK-positive non-small cell lung cancer: Japanese subgroup analysis of CROWN
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      Abstract

      Introduction

      Lorlatinib, a third-generation ALK inhibitor, showed improved efficacy versus crizotinib in patients with previously untreated, advanced ALK-positive non-small cell lung cancer in the ongoing, global, randomized, phase 3 CROWN study.

      Methods

      The study’s primary endpoint was progression-free survival assessed by blinded independent central review. Secondary endpoints included objective and intracranial response. Here, we report efficacy and safety data of the Japanese subgroup of the CROWN study (lorlatinib 100 mg once daily, n=25; crizotinib 250 mg twice daily, n=23).

      Results

      Progression-free survival was not reached (95% CI, 11.3 months-not reached) for lorlatinib and 11.1 months (95% CI, 5.4-14.8) for crizotinib (hazard ratio, 0.44; 95% CI, 0.19-1.01). Objective response (lorlatinib versus crizotinib) was 68.0% (95% CI, 46.5-85.1) versus 52.2% (95% CI, 30.6-73.2) in all patients, and intracranial response was 100.0% (3/3; 95% CI, 29.2-100.0) versus 28.6% (2/7; 95% CI, 3.7-71.0) in patients with brain metastases at baseline. The most common adverse events with lorlatinib were hypertriglyceridemia, hypercholesterolemia, and weight increased; 28.0% and 8.0% of patients had cognitive and mood effects (all grade 1/2), respectively. Lorlatinib was associated with more grade 3/4 events than crizotinib (80.0% versus 72.7%). Treatment was discontinued due to adverse events in 16.0% and 27.3% of patients in the lorlatinib and crizotinib groups, respectively.

      Conclusions

      The efficacy and safety of lorlatinib in the Japanese subgroup were similar to those in the CROWN global population, demonstrating improved outcomes versus crizotinib in Japanese patients with previously untreated, advanced ALK-positive non-small cell lung cancer.

      ClinicalTrials.gov identifier

      NCT03052608

      Keywords

      Abbreviations:

      AE (adverse event), ALK (anaplastic lymphoma kinase), BICR (blinded independent central review), CI (confidence interval), CNS (central nervous system), HR (hazard ratio), NR (not reached), NSCLC (non-small cell lung cancer), OR (odds ratio), PFS (progression-free survival), TKI (tyrosine kinase inhibitor)

      Article info

      Publication history

      Accepted: January 24, 2023
      Received in revised form: January 23, 2023
      Received: November 4, 2022

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      Author email addresses:

      Hidetoshi HAYASHI: [email protected]

      Shunsuke TERAOKA: [email protected]

      Yasushi GOTO: [email protected]

      Toru KUMAGAI: [email protected]

      Makoto NISHIO: [email protected]

      Shunichi SUGAWARA: [email protected]

      Satoshi OIZUMI: [email protected]

      Masakazu MATSUMURA: [email protected]

      Masayuki OKURA: [email protected]

      Gerson PELTZ: [email protected]

      Terufumi KATO: [email protected]

      Funding Information

      This study was sponsored by Pfizer Inc.

      Role of the Funding Source

      The study was designed by the sponsor, study investigators, and members of the steering committee. Data were collected by investigators and analyzed by the sponsor. All authors, including those employed by the sponsor of the study, contributed to the interpretation of the data and the development, writing, and approval of the manuscript. Medical writing support was funded by the sponsor. All authors had full access to the raw data in the study, and the corresponding author had final responsibility for the decision to submit for publication.

      Disclosure Statement

      Hidetoshi Hayashi reports contracted/support research grants AstraZeneca K.K., Astellas Pharma Inc., MSD K.K., Ono Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Pfizer Japan Inc., Bristol Myers Squibb Company, Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Merck Serono Co., Ltd,/ Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co. Ltd., SymBio Pharmaceutical Limited., AbbieVie Inc., inVentiv Health Japan, ICON Japan K.K., GRITSONE ONCOLOGY. Inc, PAREXEL International Copr, Kissei Pharmaceutical Co., Ltd., EPS Corporation, Syneous Health, Pfizer R&D Japan G.K., A2 Healthcare Corp, Quintilies Inc. / IQVIA Services JAPAN K.K., EP-CRSU CO., LTD, Linical Co., Ltd, Eisai Co., Ltd, CMIC Shift Zero K.K., Kyowa Hakko Kirin Co., Ltd, Bayer Yakuhin, Ltd, EPS International Co., Ltd and Otsuka Pharmaceutical Co., Ltd; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca K.K., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co. Ltd and Pfizer Japan Inc; and scholarship endowment from Bristol-Myers Squibb Co. Ltd, Chugai Pharmaceutical Co. Ltd and Ono Pharmaceutical Co. Ltd. Shunsuke Teraoka reports honoraria from AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Pfizer R&D Japan G.K. and Taiho Pharmaceutical Co Ltd.; and participated on a Data Safety Monitoring Board or Advisory Board for Pfizer R&D Japan G.K. Yasushi Goto reports honoraria from Eli Lilly, Chugai,Taiho, Boehringer Ingelheim, Ono, Bristol Myers Squibb, Pfizer, MSD, Novartis, Merck and Thermo Fischer; grants from Abbvie, Eli Lilly, Pfizer, Bristol Myers Squibb, Ono, Novartis, Kyorin, Daiichi Sankyo, Novartis, Preferred Network; participated on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Chugai, Boehringer Ingelheim, Eli Lilly, Taiho, Pfizer, Novartis, Guardant Health Inc., Illumina, DaiichiSankyo, Ono Pharmaceutical, Bristol Myers Squibb and MSD; and a leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for Cancer Net Japan and JAMT. Toru Kumagai reports honoraria from Ono Pharmaceutical, Bristol Myers Squibb K.K, Chugai Pharmaceutical Co Ltd., Eli Lilly and Company Japan K.K., AstraZeneca K.K., MSD K.K., Taiho Pharmaceutical Co. Ltd., Novartis Pharma K.K., and Pfizer Inc.; and grants from MSD K.K., AstraZeneca K.K., Ono Pharmaceutical, Chugai Pharmaceutical Co., Ltd., Eli Lilly and Company Japan K.K., Novartis Pharma K.K., Parexel International Corporation, Nippon Boehringer lngelheim Co., Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Japan Inc., Merck Biopharma Co. Ltd., Taiho Pharmaceutical Co., Ltd, Delta-Fly Pharma, Inc., IQVIA Services Japan K.K., AbbVie GK, and Nippon Kayaku Co., Ltd. Makoto Nishio reports honoraria from Ono Pharmaceuticals, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo, Lilly, AstraZeneca, MSD, AbbVie, Takeda, Pfizer, Boehringer Ingelheim, Novartis, Nippon Kayaku, Merck, and Janssen. Shunichi Sugawara reports honoraria from Pfizer, Inc., Chugai Pharmaceutical, MSD K.K., AstraZeneca, Ono Pharmaceutical, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Taiho Pharmaceutical, Eli Lilly and Company, Novartis, Kyowa Kirin, Yakult Honsha, Takeda, Nippon Kayaku, Merck, Amgen, AbbVie, Otsuka, Thermo Fisher Scientific, and Towa Pharmaceutical. Satoshi Oizumi reports honoraria from AstraZeneca, MSD and Eli Lilly; and grants from commissioned/joint research from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical, Kissei Pharmaceutical, Ono Pharmaceutical, Pfizer, Merck Biopharma, Sanofi, Taiho Pharmaceutical, and Takeda Pharmaceutical. Masakazu Matsumura and Okura Masayuki are employees of Pfizer. Gerson Peltz is a former employee of Pfizer and holds Pfizer stock/stock options. Terufumi Kato reports honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Merck Biopharma, MSD, Novartis, Ono, Pfizer and Roche; grants from commissioned/joint research from Abbvie, Amgen, AstraZeneca, Blueprint, Chugai, Eli Lilly, Haihe, Merck Biopharma, MSD, Novartis, Pfizer, Regeneron and Takeda; participated on a Data Safety Monitoring Board or Advisory Board for Abbvie, Amgen, AstraZeneca, Beigene, Chugai, Daiichi-Sankyo, Eli Lilly, Glaxo, Merck Biopharma, MSD, Nippon Kayaku, Novartis, Ono, Pfizer, Taiho and Takeda; and other financial or non-financial interests with Eli Lilly (spouse). All authors received funding for conduct of the study and medical writing support from Pfizer Inc.

      Identification

      DOI: https://doi.org/10.1016/j.jtocrr.2023.100471

      Copyright

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

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