CROWN 5-Year Subgroup Analysis Shows PFS Is Consistent With Overall Patient Population

Progression-free survival (PFS) remains unreached in the subgroup of Asian patients in the CROWN study, according to 5-year follow-up data that shows the results of this subgroup “continue to be consistent with those in the overall population.”

Yi-Long Wu, MD, of the Guangdong Lung Cancer Institute at Guangdong Provincial People’s Hospital, and colleagues conducted the study and published their findings in the Journal of Thoracic Oncology.

It was important to conduct the long-term follow-up analysis because the third-generation ALK inhibitor lorlatinib previously showed significantly longer PFS than crizotinib in the phase 3 CROWN trial, which evaluated patients with previously untreated advanced ALK-positive non–small cell lung cancer (NSCLC). The CROWN study had shown that “efficacy was similar in the Asian subgroup.”  Investigators in the CROWN study randomly assigned this subgroup of patients to receive lorlatinib 100 mg once daily (n=59) or crizotinib 250 mg twice daily (n=61). The post hoc analysis by Dr. Wu and colleagues “presents updated investigator-assessed efficacy outcomes, safety, and biomarker analyses.”

After a median follow-up of 62.4 months, the median PFS was not reached in patients receiving lorlatinib (95% CI, 64.3 months to not reached). Among the patients receiving crizotinib with a median follow-up of 55.1 months, the median PFS was 9.2 months (95% CI, 7.2 to 12.7). The hazard ratio (HR) for PFS was 0.22 (95% CI, 0.13-0.37).

The 5-year PFS rate was 63% (95% CI, 49-74) among patients receiving lorlatinib, compared with 7% in those receiving crizotinib (95% CI: 2-17). The objective response rate (ORR) was also higher in patients receiving lorlatinib (81%; 95% CI, 69-90) than in those receiving crizotinib (59%; 95% CI, 46-71).

Among patients who had brain metastases at baseline, the intracranial ORR was also higher in patients receiving lorlatinib (69%; 95% CI, 39-91) than in those receiving crizotinib (6%; 95% CI, <1-30). The median time to intracranial progression was not reached (95% CI, not reached to not reached) in patients receiving lorlatinib and was 14.6 months in those receiving crizotinib (95% CI: 9.2-27.4). with a HR of 0.01 (95% CI, <0.01-0.11). The follow-up data also showed that the subgroup’s safety profiles “were consistent with the entire population,” according to Dr. Wu and colleagues.

“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,” Dr. Wu and colleagues concluded.

Reference

Wu YL, Kim HR, Soo RA, et al. First-line lorlatinib versus crizotinib in Asian patients with advanced ALK-positive NSCLC: 5-year outcomes from the CROWN study. Journal of Thoracic Oncology. Published online February 1, 2025. doi:https://doi.org/10.1016/j.jtho.2025.02.021