We present efficacy and safety data of Asian vs non-Asian patients (pts) in the global phase III ALEX study of ALC (600 mg BID) vs CRZ (250 mg BID) in treatment-naïve advanced ALK+ NSCLC.
Pts aged ≥18 years were randomised 1:1 to receive ALC or CRZ until progression, toxicity, withdrawal or death. Race was a randomisation stratification factor. The primary endpoint was investigator (INV)-assessed progression-free survival (PFS). Secondary endpoints were: Independent Review Committee (IRC)-assessed PFS, time to central nervous system (CNS) progression, objective response rate (ORR) by INV, overall survival (OS) and safety.
In total, 303 pts were randomised (ALC N = 152 [N = 69 Asian, N = 83 non-Asian]; CRZ N = 151 [N = 69 Asian, N = 82 non-Asian]). Baseline characteristics were consistent between Asian and non-Asian subgroups, except median weight. Efficacy and safety data were similar between subgroups (table). PFS by INV was longer with ALC in Asian (HR 0.46) and non-Asian (HR 0.49) pts. Median OS has not yet been reached in either subgroup but data are immature: Asian HR 0.68, non-Asian HR 0.82. Rate of treatment discontinuation due to adverse events (AE): Asian 13.0% ALC, 11.6% CRZ; non-Asian 9.6% ALC, 13.4% CRZ. AE profiles of Asian and non-Asian subgroups were consistent with the ITT population. Diarrhoea was more common with CRZ in both subgroups vs ALC (Asian 15.0% ALC, 39.1% CRZ; non-Asian 10.0% ALC, 50.0% CRZ). Nausea was more common with CRZ in both subgroups vs ALC (Asian 10.1% ALC, 42.0% CRZ; non-Asian 17.0% ALC, 52.4% CRZ) and was more common in non-Asian vs Asian pts. Pharmacokinetics data of the subgroups will be presented.
Efficacy and safety data were similar between Asian and non-Asian pts for ALC or CRZ. The results confirm ALC 600 mg BID dosage is more effective than CRZ in Asian and non-Asian pts, and has an acceptable safety profile in Asian pts.
Clinical trial identification
Legal entity responsible for the study
F. Hoffmann-La Roche
F. Hoffmann-La Roche Ltd.
T.S.K. Mok: Consultant (Participated in Advisory Boards for the last two years): AstraZeneca, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis Oncology, BMS, Eisai and Taiho. S. Peters: Education grants, provided consultation, attended advisory boards and/or provided lectures for the following organizations: Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, Eli Lilly, F. Hoffmann-La Roche, Janssen, Merck Sharp and Dohme and Merck Serono, Pfizer, Regeneron and Takeda. D.R. Camidge: Roche Genetech, Genoptix, G1 Therapeutics, Orion, Clovis, Ariad, Novartis, Celgene, Array, Abbvie, Eli Lilly. S-H.I. Ou: Corporate-sponsored research to institutions: Pfizer, Roche, Astra Zeneca, ARIAD, Ignyta and other substantive relationships including: Pfizer, Roche, Astra Zeneca, ARIAD, Ignyta and Foundation Medicine. J.S. Ahn: Personal fees from BMS, Eisai, Janssen, Roche, Menarini and Boehringer Ingelheim, B.C. Cho: Research funding: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST; Consulting role: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Yuhan, Pfizer, Eli Lilly. S.L. Geater: Funding to institute for clinical research: Astra Zaneca, Boehringer Ingelheim, Novartis, Samsung, Roche, J. Ho: Speaker’s honorarium and research funding from Roche. A. Zeaiter: Employment at F. Hoffmann-La Roche. B. Balas: Employee and stockholder at F. Hoffmann-La Roche Ltd. E. Nueesch, E. Mitry: Employee at F. Hoffmann-La Roche, P.N. Morcos: Employment and stock ownership at F. Hoffmann-La Roche. All other authors have declared no conflicts of interest.
Efficacy and safety data by subgroups
|Asian (N = 138)||Non-Asian (N = 165)|
|ALC (N = 69)||CRZ (N = 69)||ALC (N = 83)||CRZ (N = 82)|
|Median PFS (95% CI), INV||NE (14.7–NE)||10.9 (8.6–16.4)||NE (14.0–NE)||11.1 (8.8–14.6)|
|HR (95% CI) P-value||0.46 (0.28–0.75) 0.0013||0.49 (0.32–0.75) 0.0009|
|Median PFS (95% CI), IRC||25.7 (14.7–NE)||10.8 (7.5–16.4)||NE (14.6–NE)||9.8 (7.3–16.7)|
|HR (95% CI) P-value||0.49 (0.30–0.79) 0.0026||0.56 (0.36–0.87) 0.0091|
|CNS progression 12-month cumulative incidence, % (95% CI)||9.0 (3.6–17.4)||44.9 (32.3–56.7)||9.6 (4.5–17.2)||38.4 (27.6–49.1)|
|Cause-specific HR (95% CI)||0.20 (0.10–0.42)||0.13 (0.06–0.29)|
|ORR, % (95% CI), INV||81.2 (69.94–89.57)||76.8 (65.09–86.13)||84.3 (74.71–91.39)||74.4 (63.56–83.40)|
|Most frequent AE, n (%) Nausea Diarrhoea Constipation Vomiting Fatigue Increased ALT Increased AST Dyspnoea Dizziness||7 (10.1) 10 (15.0) 28 (41.0) 7 (10.1) 14 (20.3) 15 (22.0) 14 (20.3) 2 (3.0) 8 (11.6)||29 (42.0) 27 (39.1) 29 (42.0) 33 (48.0) 5 (7.2) 26 (38.0) 20 (29.0) 2 (3.0) 13 (19.0)||14 (17.0) 8 (10.0) 24 (29.0) 4 (5.0) 15 (18.1) 8 (10.0) 7 (8.4) 7 (8.4) 4 (5.0)||43 (52.4) 41 (50.0) 20 (24.4) 25 (31.0) 20 (24.4) 19 (23.2) 17 (21.0) 5 (6.1) 8 (10.0)|
INV, investigator; IRC, Independent Review Committee; HR, hazard ratio; CNS, central nervous system; CI, confidence interval; AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase