Asian Subgroup Analysis of the Randomized Phase 3 CROWN Study of First-Line Lorlatinib Versus Crizotinib in Advanced ALK-Positive NSCLC

Qing Zhou, MD, PhD; Ross A. Soo, MBBS, PhD; Gee-Chen Chang, MD, PhD; Chao-Hua Chiu, MD; Hidetoshi Hayashi, MD, PhD; Sang-We Kim, MD, PhD; Shunsuke Teraoka, MD; Yasushi Goto, MD, PhD; Jianying Zhou, MD; Victor Ho-Fun Lee, MD; Dong-Wan Kim, MD, PhD; Baohui Han, MD, PhD; James Chung Man Ho, MD, FRCP; Chia-Chi Lin, MD, PhD; Shun Lu, MD; Anna Polli, BS; Anna Maria Calella, PhD; Jean-François Martini, PhD; Chew Hooi Wong, PhD; Tony Mok, MD; Hye Ryun Kim, MD, PhD; Yi-Long Wu, MD

JTO Clinical and Research Reports (May 2023)

Asian Subgroup Analysis of the Randomized Phase 3 CROWN Study of First-Line Lorlatinib Versus Crizotinib in Advanced ALK-Positive NSCLC

Qing Zhou, MD, PhD,
Ross A. Soo, MBBS, PhD,
Gee-Chen Chang, MD, PhD,
Chao-Hua Chiu, MD,
Hidetoshi Hayashi, MD, PhD,
Sang-We Kim, MD, PhD,
Shunsuke Teraoka, MD,
Yasushi Goto, MD, PhD,
Jianying Zhou, MD,
Victor Ho-Fun Lee, MD,
Dong-Wan Kim, MD, PhD,
Baohui Han, MD, PhD,
James Chung Man Ho, MD, FRCP,
Chia-Chi Lin, MD, PhD,
Shun Lu, MD,
Anna Polli, BS,
Anna Maria Calella, PhD,
Jean-François Martini, PhD,
Chew Hooi Wong, PhD,
Tony Mok, MD,
Hye Ryun Kim, MD, PhD,
Yi-Long Wu, MD

Affiliations

Qing Zhou, MD, PhD: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical Sciences, Guangzhou, People’s Republic of China
Ross A. Soo, MBBS, PhD: National University Cancer Institute, Singapore
Gee-Chen Chang, MD, PhD: School of Medicine and Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
Chao-Hua Chiu, MD: Taipei Cancer Center and Taipei Medical University Hospital, Taipei, Taiwan
Hidetoshi Hayashi, MD, PhD: Kindai University Faculty of Medicine, Osaka, Japan
Sang-We Kim, MD, PhD: Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Shunsuke Teraoka, MD: Wakayama Medical University, Wakayama, Japan
Yasushi Goto, MD, PhD: National Cancer Center Hospital, Tokyo, Japan
Jianying Zhou, MD: First Affiliated Hospital of Zhejiang University, Hangzhou, People’s Republic of China
Victor Ho-Fun Lee, MD: University of Hong Kong, Hong Kong
Dong-Wan Kim, MD, PhD: Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
Baohui Han, MD, PhD: Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
James Chung Man Ho, MD, FRCP: University of Hong Kong, Hong Kong
Chia-Chi Lin, MD, PhD: National Taiwan University Hospital, Taipei, Taiwan
Shun Lu, MD: Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
Anna Polli, BS: Pfizer Inc., Milan, Italy
Anna Maria Calella, PhD: Pfizer Inc., Milan, Italy
Jean-François Martini, PhD: Pfizer Global Product Development-Oncology, La Jolla, California
Chew Hooi Wong, PhD: Pfizer Pte. Ltd., Singapore
Tony Mok, MD: State Key Laboratory of Translational Oncology and Chinese University of Hong Kong, Hong Kong
Hye Ryun Kim, MD, PhD: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
Yi-Long Wu, MD: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical Sciences, Guangzhou, People’s Republic of China; Corresponding author. Address for correspondence: Yi-Long Wu, MD, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 106 Zhongshan Er Road, Guangzhou, Guangdong 510080, People’s Republic of China.

Journal volume & issue: Vol. 4, no. 5
p. 100499

Abstract

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Introduction: Lorlatinib is a potent, third-generation inhibitor of ALK. In the planned interim analysis of the ongoing, phase 3, randomized, global CROWN trial (NCT03052608), lorlatinib resulted in significantly longer progression-free survival than crizotinib in patients with previously untreated, advanced, ALK-positive NSCLC. 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 end point was progression-free survival assessed by blinded independent central review. Objective response rate (ORR), intracranial ORR, safety, and select biomarkers were secondary end points. 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 blinded independent central review or death: 0.40; 95% CI: 0.23–0.71). ORR was 78% (95% CI: 65–88) versus 57% (95% CI: 44–70) for patients treated with lorlatinib and crizotinib, respectively. In patients with measurable, nonmeasurable, or both measurable and nonmeasurable brain metastases at baseline, intracranial ORR was 73% (95% CI: 39–94) versus 20% (95% CI: 4–48) for patients treated with lorlatinib and crizotinib, respectively. The definition of nonmeasurable brain metastases is: a brain lesion less than 10 mm in MRI scan is defined as nonmeasurable brain metastasi based on RECIST criteria (Clinical trial evaluation criteria). Hypercholesterolemia, hypertriglyceridemia, and edema were the most frequently reported adverse events with lorlatinib. Conclusions: Lorlatinib efficacy and safety in the Asian subgroup of CROWN were consistent with those in the overall population.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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