5-year update of CROWN study shows benefit of lorlatinib over crizotinib

MedNet.nl: Lorlatinib as first-line treatment for advanced ALK-positive NSCLC improves PFS compared with crizotinib. The 5-year follow-up showed that the median progression-free survival in the lorlatinib arm had not yet been reached, while that in the crizotinib arm was 9.1 months. Never before has a study in advanced NSCLC seen such a long median progression-free survival, researchers from the CROWN study told the ASCO conference. The phase 3 CROWN study included 296 previously untreated patients with advanced ALK-positive NSCLC. They were randomized to lorlatinib (n=149) or crizotinib (n=147). Previously presented study results showed that lorlatinib significantly reduced the risk for progression or death compared with crizotinib (HR=0.28). In Chicago, the researchers showed that after a median follow-up of 60.2 months, median progression-free survival (PFS) had not yet been reached in the lorlatinib arm. In the crizotinib arm, it was 9.1 months (HR=0.19). After 60 months, 60% and 8% of patients were progression-free, respectively. At the time of data analysis, 74 patients were still being treated in the lorlatinib arm and nine patients in the crizotinib arm. Overall survival could not yet be analyzed due to an insufficient number of deaths. Benefit of treatment with lorlatinib was seen in all subgroups, including patients with brain metastases. After 5 years, intracranial PFS in the lorlatinib arm was 92%. The updated analysis found no new treatment-related adverse events. Grade 3/4 adverse events occurred in 77% versus 57% of patients in the lorlatinib and crizotinib arms. The researchers concluded that the long-term efficacy and absence of new safety signals represent an unprecedented improvement in outcomes for patients with advanced ALK-positive NSCLC. During a discussion of the study results, the commentator said that the fact that new brain metastases are largely absent with treatment with lorlatinib is particularly relevant, given that brain metastases do occur to some extent with second-generation ALK inhibitors. Solomon BJ, Liu G, Felip E, et al. Lorlatinib vs crizotinib in treatment-naïve patients with advanced ALK+ non-small cell lung cancer: 5-year progression-free survival and safety from the CROWN study. ASCO 2024, abstract LBA 8503. Shaw AT, Bauer TM, De Marinis F, et al. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med 2020;383:2018-29. This article was originally published in Dutch on MedNet.nl

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5-year update of CROWN study shows benefit of lorlatinib over crizotinib

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