Lorlatinib versus crizotinib as first-line treatment for advanced ALK positive non-small cell lung cancer: 7-year update from the phase 3 CROWN study
Mené sur 296 patients atteints d'un cancer du poumon non à petites cellules ALK+ de stade avancé, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression à 7 ans, et la toxicité du lorlatinib et du crizotinib en traitement de première ligne
Background: Due to the unprecedented PFS benefit with lorlatinib after 5 years of follow-up in the phase 3 CROWN study, we aimed to quantify long-term outcomes at 7 years.
Patients and methods: 296 treatment-naive patients with advanced ALK-positive NSCLC were randomized 1:1 to receive lorlatinib 100 mg OD (n=149) or crizotinib 250 mg BID (n=147). This post hoc analysis presents investigator-assessed efficacy outcomes, safety, and biomarker analyses.
Results: With median follow-up of 83.0 and 77.2 months, median PFS (95% CI) was not reached (NR; 68.5-NR) with lorlatinib and 9.1 months (7.4-10.9) with crizotinib (HR, 0.19; 95% CI, 0.13-0.26); 7-year PFS was 55% and 3% respectively. With lorlatinib, patients without a PFS event at the end of 24 months had a 79% probability of survival without progression at year 7. No new intracranial progression events occurred after the first 30 months on lorlatinib. Median time to intracranial progression (95% CI) was NR (NR-NR) with lorlatinib and 16.4 months (12.7-21.9) with crizotinib (HR, 0.06; 95% CI, 0.03-0.12). Overall survival follow-up is ongoing; the number of events for a protocol-specified analysis has not been met. The safety profile was consistent with the 5-year results. With lorlatinib, treatment-related AEs did not lead to discontinuations after the first 26 months. More genetic alterations were detected in ctDNA samples from early progressors than in long-term responders on lorlatinib; new potential resistance mechanisms were identified.
Conclusions: With median PFS yet to be reached after 7 years of follow-up in CROWN, lorlatinib continues to show unprecedented long-term benefit in patients with advanced ALK-positive NSCLC. Patients without progression within 24 months on lorlatinib have a low risk of progression or death at year 7 and may continue long-term treatment. Findings suggest that sustained long-term disease control with first-line lorlatinib may enable advanced ALK-positive NSCLC to evolve toward a chronic condition.
Annals of Oncology , résumé, 2026