Presidential Session 3

LBA8_PR - KEYNOTE-048: Phase 3 study of first-line pembrolizumab (P) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC)

LBA9_PR - Cetuximab versus cisplatin in patients with HPV-positive, low risk oropharyngeal cancer, receiving radical radiotherapy

LBA10 - Primary results of ALESIA: A randomised, phase III, open-label study of alectinib vs crizotinib in Asian patients with treatment-naïve ALK+ advanced NSCLC


The highly selective, central nervous system (CNS)-active, ALK inhibitor alectinib, showed superior efficacy and lower toxicity than crizotinib in patients with treatment-naïve ALK+ NSCLC in the global phase III ALEX study (NCT02075840; PFS hazard ratio [HR] 0.47, 95% CI 0.34–0.65, p<0.001): median PFS not estimable alectinib vs 11.1 months crizotinib. Updated data from ALEX (cut-off date Dec 1, 2017), revealed a PFS HR of 0.43, 95% CI 0.32–0.58, with a median PFS of 34.8 months alectinib vs 10.9 months crizotinib [Camidge et al. ASCO 2018]. We will present primary results from the randomised, open-label, phase III ALESIA study comparing the efficacy and safety of first-line alectinib versus crizotinib in Asian patients with advanced ALK+ NSCLC (NCT02838420). The objective of the study is to determine whether the PFS benefit of alectinib in Asian patients is consistent with the benefit observed in the global ALEX study.
Alectinib (ALC), a highly selective CNS-active ALK inhibitor, showed superior efficacy vs crizotinib (CRZ) in treatment-naïve ALK+ NSCLC in the global phase III ALEX study (PFS HR 0.47, 95% CI 0.34–0.65, p<0.001). At an updated data cutoff, the PFS HR was 0.43, 95% CI 0.32–0.58, median PFS 34.8 months ALC vs 10.9 months CRZ. We report primary results from the phase III ALESIA study of first-line ALC vs CRZ in Asian patients with advanced ALK+ NSCLC using the global ALC dose (NCT02838420).

Patients had ALK+ stage IIIB/IV NSCLC (by central IHC testing) and ECOG PS 0–2. Asymptomatic CNS metastases were allowed. Patients were randomised 2:1 to receive ALC 600mg BID (n=125) or CRZ 250mg BID (n=62). Regular tumour/CNS imaging was performed. Primary endpoint: PFS by INV (RECIST v1.1). Primary objective: consistency with the PFS benefit seen in ALEX. Secondary endpoints: PFS by IRC, time to CNS progression, ORR, DOR, OS, CNS ORR, QoL and safety.

Median duration of follow-up was 16.2 months ALC vs 15.0 months CRZ. At the primary data cutoff (May 31, 2018), ALC significantly reduced the risk of progression/death (INV PFS) vs CRZ: HR 0.22, 95% CI 0.13–0.38, p<0.0001; median PFS not estimable (NE) ALC vs 11.1 months CRZ. Secondary endpoints supported the primary endpoint: IRC PFS, HR 0.37 (95% CI 0.22–0.61; p<0.0001); median PFS NE ALC vs 10.7 months CRZ; time to CNS progression (IRC) cause-specific HR 0.14 (95% CI 0.06–0.30; p<0.0001); ORR (INV), 91.2% ALC vs 77.4% CRZ, p=0.0095; DOR (INV), HR 0.22 (95% CI 0.12–0.40), p<0.0001; median DOR NE ALC vs 9.3 months CRZ; OS data immature: HR 0.28 (95% CI 0.12–0.68), p=0.0027, event rate ALC 6.4% vs CRZ 21.0%; median OS NE both arms; CNS ORR (IRC) in patients with measurable/non-measurable CNS baseline lesions, 72.7% ALC vs 21.7% CRZ (50.0% vs 13.0% complete response). Despite longer treatment duration (14.7 ALC vs 12.6 months CRZ), fewer ALC patients had grade 3–5 AEs (29% vs 48% CRZ), serious AEs (15% vs 26%) or AEs leading to treatment discontinuation (7% vs 10%).

ALESIA study results are consistent with the global ALEX study and confirm the clinical benefit of ALC in Asian patients with advanced ALK+ NSCLC.

Clinical trial identification