Background
Phase III, open-label RCT (J-ALEX). N=207. Stage IIIB–IV or recurrent ALK-positive NSCLC (ALK IHC), ECOG PS 0–2, 0–1 prior chemotherapy lines (no prior ALK inhibitor), Japanese patients. First-line alectinib vs crizotinib. Stratified by ECOG PS, prior treatment line, and study site.
Interventions and follow up
Arm A: Alectinib 300 mg PO BID (Japanese approved dose) (N=103)
Arm B: Crizotinib 250 mg PO BID (N=104)
Primary endpoint: PFS by independent review
mFollow up: ~12 mo (interim primary analysis)
Arm B: Crizotinib 250 mg PO BID (N=104)
Primary endpoint: PFS by independent review
mFollow up: ~12 mo (interim primary analysis)
Results
mPFS: NR vs 10.2 mo, HR 0.34 (95% CI 0.17–0.70; P<.0001) at interim
3-yr PFS (updated): 62% vs 39%
ORR: 91.9% vs 78.8%
CNS response: Significantly improved with alectinib
3-yr PFS (updated): 62% vs 39%
ORR: 91.9% vs 78.8%
CNS response: Significantly improved with alectinib
Adverse events
Overall: Grade ≥3 AEs 26.2% (alectinib) vs 51.9% (crizotinib)
Alectinib-specific: Bradycardia (all grades 8%), elevated CK 7.8%, constipation
Crizotinib-specific: Nausea 69% (all grades), visual disturbance, QTc prolongation
Alectinib-specific: Bradycardia (all grades 8%), elevated CK 7.8%, constipation
Crizotinib-specific: Nausea 69% (all grades), visual disturbance, QTc prolongation
Conclusions
Alectinib demonstrated superior PFS (HR 0.34) and substantially better tolerability vs crizotinib in Japanese ALK-positive NSCLC, establishing it as the preferred ALK inhibitor in Japan and providing the first head-to-head randomized evidence for alectinib superiority.
Key Limitations
Japanese-only trial using alectinib 300 mg BID (half the Western dose used in ALEX, 600 mg BID), limiting global generalizability and PK/PD comparability. Crizotinib comparator no longer standard. OS immature. Small sample. Now largely superseded by CROWN (lorlatinib) in 1L for fit patients.
Clinical Context
J-ALEX was the first RCT demonstrating alectinib superiority over crizotinib, published with the global ALEX trial. Together they established alectinib as the preferred 1L ALK inhibitor over crizotinib. Japanese standard dose is 300 mg BID; global standard 600 mg BID. Lorlatinib (CROWN) increasingly preferred 1L in fit patients. ESMO-MCBS score 5 vs crizotinib.