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 MokHye Ryun Kim, Yi Long Wu

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4 Citations (Scopus)

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.

Original languageEnglish
Article number100499
JournalJTO Clinical and Research Reports
Volume4
Issue number5
DOIs
Publication statusPublished - May 2023

Keywords

  • Anaplastic lymphoma kinase
  • Lorlatinib
  • Non–small cell lung cancer
  • Phase 3
  • Progression-free survival

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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