Alectinib (ALC) versus crizotinib (CRZ) in ALK-inhibitor naive ALK -positive non-small cell lung cancer ( ALK+ NSCLC): Primary results from the J-ALEX study.
2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2016.34.15_suppl.9008
ISSN1527-7755
AutoresHiroshi Nokihara, Toyoaki Hida, Masashi Kondo, Young Hak Kim, Koichi Azuma, Takashi Seto, Yuichi Takiguchi, Makoto Nishio, Hiroshige Yoshioka, Fumio Imamura, Katsuyuki Hotta, Satoshi Watanabe, Kōichi Goto, Kazuhiko Nakagawa, Tetsuya Mitsudomi, Nobuyuki Yamamoto, Hiroshi Kuriki, Ryoichi Asabe, Tomohiro Tanaka, Tomohide Tamura,
Tópico(s)Colorectal Cancer Treatments and Studies
Resumo9008 Background: ALC showed promising efficacy and tolerability in the phase I/II study (AF-001JP). Here, we conducted the randomized open-label phase III trial (J-ALEX study, JapicCTI-132316) to prove superior progression-free survival (PFS) of ALC to CRZ in ALK+ NSCLC patients (pts) without prior ALK inhibitor treatment. Methods: ALK+ NSCLC pts were randomized 1:1 either to receive ALC (300 mg b.i.d.) or CRZ (250 mg b.i.d.) and stratified by ECOG PS (0/1 vs 2), treatment line (1st vs 2nd), and clinical stage (IIIB/IV vs recurrence). Treatment on both arms was continued until disease progression or unacceptable toxicity. Primary endpoint was PFS according to the blinded independent review board. Secondary endpoints included overall survival, objective response rate, and safety. Under an assumption of expected hazard ratio (HR) of 0.643, 164 events were required to have 80% power with 2-sided alpha of 0.05. Three interim analyses (IA) for early stopping due to efficacy were planned after 33%, 50%, and 75% of required PFS events occurred. Results: 207 pts were enrolled at 41 centers in Japan between November 2013 and August 2015. 98%, 73%, and 64% of the pts were PS0-1, stage IV, and 1st line, respectively. A second IA was performed on 6thFebruary 2016. Independent data monitoring committee recommended the release of study data because the superiority in PFS had been demonstrated. The PFS HR of ALC arm to CRZ arm was 0.34 (99.6826% CI: 0.17-0.70, stratified log-rank p 30% frequency, while in the CRZ arm nausea (74%), diarrhea (73%), vomiting (59%), visual disturbance (55%), dysgeusia (52%), constipation (46%), ALT elevation (32%), and AST elevation (31%) were seen in >30% pts. Grade 3-4 AEs occurred with greater frequency in the CRZ arm (ALC arm: 27% vs CRZ arm: 51%). There were no treatment-related deaths in either arm. Conclusions: At J-ALEX IA, ALC demonstrated significantly prolonged PFS compared with CRZ and was well tolerated with a favorable AE profile. Clinical trial information: JapicCTI-132316.
Referência(s)