Alectinib是一种靶向ALK的TKI，在未使用crizotinib或对crizotinib耐药的ALK阳性非小细胞肺癌患者中表现出强大的疗效。J-ALEX在日本crizotinib-naive的ALK阳性NSCLC患者中显示alectinib 300mg BID优于crizotinib，其中progression-free survival [PFS] HR 0.34, p<0.0001。我们报告ALEX研究的主要结果，该研究对照alectinib 600mg BID和crizotinib一线治疗晚期ALK阳性的非小细胞肺癌患者。
Alectinib versus crizotinib in treatment-naive advancedALK-positive non-small cell lung cancer (NSCLC): Primary results of the global phase III ALEX study
Alectinib, a TKI targeting ALK, has shown robust efficacy in crizotinib-naïve/resistantALK+ NSCLC. J-ALEX showed superiority of alectinib 300mg BID vs crizotinib in Japanese pts with crizotinib-naïveALK+ NSCLC (progression-free survival [PFS] HR 0.34, p<0.0001). We report primary results from the ALEX study of first-line alectinib 600mg BID vs crizotinib in advancedALK+ NSCLC (NCT02075840).
This open-label randomized multicenter phase III study enrolled pts with stage IIIB/IVALK+ NSCLC, determined by central IHC testing. Eligible pts had ECOG PS 0–2 and no prior systemic therapy for advanced NSCLC. Pts with asymptomatic CNS metastases were allowed. Pts (n=303) were randomized 1:1 to receive alectinib 600mg or crizotinib 250mg BID. Primary endpoint: Investigator (Inv)-assessed PFS (RECIST v1.1), with systematic CNS imaging in all pts. Secondary endpoints included independent review committee (IRC)-assessed PFS, IRC-assessed time to CNS progression (TTP), objective response rate (ORR), overall survival (OS) and safety.
At the primary data cut-off (9 Feb 2017), alectinib demonstrated statistically significant superiority vs crizotinib, reducing risk of progression/death by 53% (HR 0.47, 95% CI 0.34–0.65, p<0.0001); alectinib median PFS was not reached (95% CI 17.7–NE) vs crizotinib 11.1 months (95% CI 9.1–13.1). Key secondary endpoints showed superiority for alectinib vs crizotinib, respectively: IRC PFS, HR 0.50 (95% CI 0.36–0.70; p<0.0001); median PFS 25.7 months (95% CI 19.9–NE) vs 10.4 months (95% CI 7.7–14.6); CNS TTP, cause-specific HR of CNS progression 0.16 (95% CI 0.10–0.28; p<0.0001); ORR (Inv) 83% (95% CI 76–89) vs 76% (95% CI 68–82), p=0.09; OS, based on 25% events, HR 0.76 (95% CI 0.48–1.20; p=0.24). Grade 3/4 AEs were less frequent with alectinib, 41%, vs 50% with crizotinib; fatal AEs occurred in 3% vs 5%, respectively. Rates of AEs leading to discontinuation, dose reduction and interruption were lower with alectinib.
Alectinib showed superior efficacy and favorable tolerability compared with crizotinib. ALEX results support alectinib as a new standard of care for treatment-naïveALK+ NSCLC.
F. Hoffmann-La Roche
Clinical trial information:NCT02075840