First-line lorlatinib versus crizotinib in Asian patients with advanced ALK-positive NSCLC: 5-year outcomes from the CROWN study.

in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer by Yi-Long Wu, Hye Ryun Kim, Ross A Soo, Qing Zhou, Hiroaki Akamatsu, Gee-Chen Chang, Chao-Hua Chiu, Hidetoshi Hayashi, Sang-We Kim, Yasushi Goto, Terufumi Kato, Jianying Zhou, Victor Ho-Fun Lee, Makoto Nishio, Baohui Han, Dong-Wan Kim, Shun Lu, Anna Polli, Jean-François Martini, Francesca Toffalorio, Chew Hooi Wong, Tony Mok

TLDR

  • Lorlatinib showed significantly longer progression-free survival and objective response rate compared to crizotinib in Asian patients with advanced ALK-positive non-small cell lung cancer after 5 years of follow-up.

Abstract

Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, showed significantly longer progression-free survival (PFS) than crizotinib in the phase 3 CROWN trial (NCT03052608) in patients with previously untreated advanced ALK-positive non-small cell lung cancer (NSCLC). Efficacy was similar in the Asian subgroup. We present an updated subgroup analysis in Asian patients after 5 years of follow-up. Patients were randomly (1:1) assigned to receive lorlatinib 100 mg once daily (n=59) or crizotinib 250 mg twice daily (n=61). This post hoc analysis presents updated investigator-assessed efficacy outcomes, safety, and biomarker analyses. After a median follow-up of 62.4 months for lorlatinib and 55.1 months for crizotinib, median PFS was not reached (NR; 95% confidence interval [CI]: 64.3‒NR) and 9.2 months (95% CI: 7.2‒12.7), respectively (hazard ratio [HR], 0.22; 95% CI: 0.13‒0.37); 5-year PFS was 63% (95% CI: 49-74) and 7% (95% CI: 2-17). Objective response rate (ORR) was 81% (95% CI: 69-90) with lorlatinib and 59% (95% CI: 46‒71) with crizotinib. In patients with baseline brain metastases, intracranial (IC) ORR was 69% (95% CI: 39‒91) with lorlatinib and 6% (95% CI: <1‒30) with crizotinib. Median time to IC progression was NR (95% CI: NR‒NR) and 14.6 months (95% CI: 9.2‒27.4), respectively (HR, 0.01; 95% CI: <0.01‒0.11). Safety profiles were consistent with the entire population. After 5 years of follow-up, lorlatinib efficacy and safety in the Asian subgroup of CROWN continue to be consistent with those in the overall population, with PFS remaining unreached with lorlatinib.

Overview

  • The study analyzed the efficacy and safety of lorlatinib compared to crizotinib in Asian patients with previously untreated advanced ALK-positive non-small cell lung cancer (NSCLC).
  • The study used data from the phase 3 CROWN trial, which was conducted over 5 years of follow-up.
  • The primary objective was to evaluate the progression-free survival (PFS) and objective response rate (ORR) in Asian patients receiving either lorlatinib or crizotinib.

Comparative Analysis & Findings

  • Median PFS was not reached (NR) with lorlatinib and 9.2 months with crizotinib, showing a significant advantage of lorlatinib.
  • 5-year PFS was 63% with lorlatinib and 7% with crizotinib, indicating a significantly longer duration of tumor control with lorlatinib.
  • Intracranial (IC) ORR was 69% with lorlatinib and 6% with crizotinib, and median time to IC progression was NR with lorlatinib and 14.6 months with crizotinib.

Implications and Future Directions

  • The study's findings suggest that lorlatinib may be a more effective treatment option for Asian patients with advanced ALK-positive NSCLC compared to crizotinib.
  • Future studies could investigate the long-term safety and efficacy of lorlatinib in this patient population, as well as explore its potential use in combination with other therapies.
  • The results of this study may inform treatment decisions for patients with advanced ALK-positive NSCLC and highlight the importance of considering patient demographics, such as ethnicity, when selecting a therapy.
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