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

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

doi:10.1016/j.jtocrr.2023.100499

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

JTO Clin Res Rep. 2023 Mar 11;4(5):100499. doi: 10.1016/j.jtocrr.2023.100499. eCollection 2023 May.

Authors

Qing Zhou¹, Ross A Soo², Gee-Chen Chang^{3

4

5

6}, Chao-Hua Chiu⁷, Hidetoshi Hayashi⁸, Sang-We Kim⁹, Shunsuke Teraoka¹⁰, Yasushi Goto¹¹, Jianying Zhou¹², Victor Ho-Fun Lee¹³, Dong-Wan Kim¹⁴, Baohui Han¹⁵, James Chung Man Ho¹³, Chia-Chi Lin¹⁶, Shun Lu¹⁴, Anna Polli¹⁷, Anna Maria Calella¹⁷, Jean-François Martini¹⁸, Chew Hooi Wong¹⁹, Tony Mok²⁰, Hye Ryun Kim²¹, Yi-Long Wu¹

Affiliations

¹ Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical Sciences, Guangzhou, People's Republic of China.
² National University Cancer Institute, Singapore.
³ School of Medicine and Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁴ Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁵ Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
⁶ Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
⁷ Taipei Cancer Center and Taipei Medical University Hospital, Taipei, Taiwan.
⁸ Kindai University Faculty of Medicine, Osaka, Japan.
⁹ Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
¹⁰ Wakayama Medical University, Wakayama, Japan.
¹¹ National Cancer Center Hospital, Tokyo, Japan.
¹² First Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China.
¹³ University of Hong Kong, Hong Kong.
¹⁴ Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
¹⁵ Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
¹⁶ National Taiwan University Hospital, Taipei, Taiwan.
¹⁷ Pfizer Inc., Milan, Italy.
¹⁸ Pfizer Global Product Development-Oncology, La Jolla, California.
¹⁹ Pfizer Pte. Ltd., Singapore.
²⁰ State Key Laboratory of Translational Oncology and Chinese University of Hong Kong, Hong Kong.
²¹ Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.

Abstract

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.

Keywords: Anaplastic lymphoma kinase; Lorlatinib; Non–small cell lung cancer; Phase 3; Progression-free survival.