The highly selective central nervous system (CNS)-active ALK inhibitor ALC showed superior efficacy vs CRZ in treatment-naïve ALK+ NSCLC in the global phase III ALEX study. At an updated data cut off, the PFS HR was 0.43 (95% CI 0.32–0.58), median PFS 34.8 months ALC, 10.9 months CRZ. We present results from the phase III ALESIA study of first-line ALC vs CRZ in Asian pts with advanced ALK+ NSCLC (NCT02838420).
Pts had ALK+ stage IIIB/IV NSCLC (by central IHC testing) and ECOG PS 0–2. Asymptomatic CNS metastases were allowed. Pts were randomised 2:1 to receive the global ALC dose 600mg BID or CRZ 250mg BID. Regular tumour/CNS imaging was done. Primary objective: consistent PFS benefit as seen in ALEX. Primary endpoint: PFS by investigator (INV). Secondary endpoints included: PFS by independent review committee (IRC), time to CNS progression, ORR, DOR, OS, CNS ORR, CNS DOR, QoL and safety.
Median follow-up: 16.2 months ALC, 15.0 months CRZ. At the primary data cut off (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, 11.1 months CRZ. Secondary endpoints (Table) supported the primary data. RANO, Response Assessment in Neuro-Oncology; RECIST, Response Evaluation Criteria in Solid TumoursALC (n = 125) CRZ (n = 62) P value Median PFS (IRC), months NE 10.7 <0.0001 HR 0.37 (95% CI 0.22–0.61) CNS progression without prior systemic progression (IRC), patients with events, n (%) 12 (9.6) 22 (35.5) <0.0001 cause-specific HR 0.14 (95% CI 0.06–0.30) ORR (INV), n (%) 114 (91.2) 48 (77.4) 0.0095 Median DOR (INV), months NE 9.3 <0.0001 HR 0.22 (95% CI 0.12–0.40) CNS ORR (IRC, RECIST) in pts with measurable/non-measurable CNS metastases at baseline, n (%) 32 (72.7) 5 (21.7) CNS ORR (IRC, RECIST) in pts with measurable CNS metastases at baseline, n (%) 16 (94.1) 2 (28.6) CNS ORR (IRC, RANO) in pts with measurable CNS metastases at baseline, n (%) 17 (100.0) 1 (16.7) Median CNS DOR (IRC, RECIST) in pts with measurable/non-measurable CNS metastases at baseline, months NE 3.7 HR 0.04 (95% CI < 0.01–0.25) <0.001 Median CNS DOR (IRC, RECIST) in pts with measurable CNS metastases at baseline, months NE NE HR 0.16 (95% CI 0.01–1.85) 0.0961
OS data are immature: HR 0.28 (95% CI 0.12–0.68), p = 0.0027, event rate ALC 6.4%, CRZ 21.0%; median OS NE both arms. ALC pts reported delayed time to worsening of lung cancer symptoms (HR 0.67 [95% CI 0.38–1.18]) and QoL (HR 0.48 [95% CI 0.23–1.04]), compared with CRZ pts. Despite longer treatment duration (14.7 months ALC, 12.6 months CRZ), fewer ALC pts had grade 3–5 AEs (29% vs 48% CRZ), serious AEs (15% vs 26%) or AEs leading to treatment discontinuation (7% vs 10%).
Results confirm the clinical benefit of ALC in pts with advanced ALK+ NSCLC including greater improvement in QoL and demonstrate consistency with the ALEX study.
NCT02838420.
F. Hoffmann-La Roche.
F. Hoffmann-La Roche Ltd.
C. Zhou: Honoraria: Eli Lily, Roches, BI, Hengrui. L. Bu, C. Wang, L. Yang: Roche employee. P.N. Morcos: Stock ownership in Roche. E. Mitry: Roche employee and stock ownership. All other authors have declared no conflicts of interest.