Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001
Mené sur 53 patients atteints d'un cancer du poumon non à petites cellules de stade avancé présentant des réarrangements du gène ROS1, cet essai randomisé évalue l'efficacité, du point de vue du taux de réponse objective et de la survie globale, et la toxicité du crizotinib (durée médiane de suivi : 62,6 mois)
Background : In the ongoing phase 1 PROFILE 1001 study, crizotinib showed antitumor activity in patients with ROS1-rearranged advanced non-small-cell lung cancer (NSCLC). Here, we present updated antitumor activity, overall survival (OS) and safety data (additional 46.2 months follow-up) for patients with ROS1-rearranged advanced NSCLC from PROFILE 1001. Patients and Methods : ROS1 status was determined by fluorescence in situ hybridization or reverse transcriptase–polymerase chain reaction. All patients received crizotinib at a starting dose of 250 mg twice daily. Results : Fifty-three patients received crizotinib, with a median duration of treatment of 22.4 months. At data cut-off, treatment was ongoing in 12 patients (23%). The objective response rate (ORR) was 72% (95% CI, 58–83), including 6 confirmed complete responses and 32 confirmed partial responses; 10 patients had stable disease. Responses were durable (median duration of response 24.7 months; 95% CI, 15.2–45.3). ORRs were consistent across different patient subgroups. Median progression-free survival was 19.3 months (95% CI, 15.2–39.1). A total of 26 deaths (49%) occurred (median follow-up period of 62.6 months), and of the remaining 27 patients (51%), 14 (26%) were in follow-up at data cut-off. Median OS was 51.4 months (95% CI, 29.3–not reached) and survival probabilities at 12, 24, 36, and 48 months were 79%, 67%, 53%, and 51%, respectively. No correlation was observed between overall survival and specific ROS1 fusion partner. Treatment-related adverse events (TRAEs) were mainly grade 1 or 2. There were no grade ≥4 TRAEs and no TRAEs associated with permanent discontinuation. No new safety signals were reported with long-term crizotinib treatment. Conclusions : These findings serve as a new benchmark for OS in ROS1-rearranged advanced NSCLC, and continue to show the clinically meaningful benefit and safety of crizotinib in this molecular subgroup.
Annals of Oncology 2019