ALINA

Background

Phase III, open-label RCT (ALINA). N=257. Completely resected stage IB–IIIA ALK-rearranged NSCLC (IHC/FISH/NGS), no prior ALK inhibitor or adjuvant systemic therapy. Adjuvant alectinib vs platinum chemotherapy. Stratified by stage and prior adjuvant chemotherapy.

Interventions and follow up

Arm A: Alectinib 600 mg PO BID × 2 years (N=130)
Arm B: Platinum-based chemotherapy × 4 cycles (carboplatin+pemetrexed or carboplatin+paclitaxel per histology) (N=127)
Primary endpoint: Investigator-assessed DFS
mFollow up: 27.9 mo

Results

2-yr DFS: 93.8% vs 63.0%, HR 0.24 (95% CI 0.13–0.43; P<.001)
CNS DFS: Significantly improved with alectinib
OS: Immature at primary analysis

Adverse events

Overall: Grade ≥3 AEs 30% (alectinib) vs 31% (chemo)
Alectinib-specific: Elevated CK 9.2%, bradycardia 1.5%
Chemo-specific: Neutropenia, nausea/vomiting
Discontinuation: 12% vs 18%

Conclusions

Adjuvant alectinib produced a dramatic DFS improvement vs platinum chemotherapy in resected ALK-positive NSCLC (HR 0.24; 2-yr DFS 93.8% vs 63.0%), the largest adjuvant targeted-therapy effect in NSCLC, with notable CNS protection.

Key Limitations

OS immature; DFS–OS correlation in adjuvant NSCLC unestablished. Chemotherapy-alone comparator may be suboptimal. Optimal adjuvant duration (2 yr vs longer) unresolved. Predominantly Asian population limits generalizability. Stage IB includes lower-risk patients with uncertain net benefit.

Clinical Context

FDA approved adjuvant alectinib for resected ALK+ NSCLC (April 2024), the first ALK inhibitor in the adjuvant setting. Complements ADAURA (osimertinib for EGFR+). ESMO recommends adjuvant alectinib in resected ALK+ stage IB–IIIA; ESMO-MCBS pending OS data.

References