Neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), has been approved for the indication of HER2+ MBC (N+C) and Early HER2+ BC. In a multinational, randomized, open-label, phase III trial (NALA; NCT01808573), N+C was shown to significantly extend progression free survival (PFS) and time to intervention for central nervous system (CNS) disease vs L+C in HER2+ MBC patients (pts) with ≥2 prior HER2-directed regimens. Here, we present the exploratory pan-Asian subgroup analysis from the NALA study.
Centrally confirmed HER2+ MBC pts were randomized 1:1 to N (240mg qd) + C (750mg/m2 bid, day 1-14) or L (1250mg qd) + C (1000mg/m2 bid, day 1-14) in 21-day cycles. Co-primary endpoints were centrally confirmed PFS and overall survival (OS). Secondary endpoints included intervention for CNS disease, objective response rate (ORR), duration of response (DOR), clinical benefit rate (CBR), and safety.
202 Asian pts were enrolled, 63.9% were Chinese from Taiwan and Hong Kong (n=129). In Asian pts, significant improvement in PFS (median 7.0 vs 5.4 mo, HR=0.58; p<0.001) and overall cumulative incidence of intervention for CNS disease (27.9 vs 33.8%; p=0.039) was observed for N+C vs L+C, and a positive trend in OS was noted (median: 23.8 vs 18.7 mo, HR=0.79; p=0.185). Detailed efficacy data are presented in the table. Diarrhea was the most frequent treatment-emergent adverse event for both arms (78.8% vs 51.0%). All events of treatment-emergent diarrhea were ≤ grade 3. Treatment discontinuation rates due to diarrhea were comparable in both arms (N+C vs. L+C 1.0 vs 0.0%).
Endpoints Pan-Asian N+C (n=104) L+C(n=98) HR (95% CI) PFS Median (mo) 7.0 5.4 0.58 (0.41, 0.81) K-M Estimates % (95% CI) 6 mo 53.7 (42.9, 63.3) 33.8 (23.9, 43.8) 12 mo 33.5 (23.4, 43.9) 10.0 (4.4, 18.6) 18 mo 19.9 (11.2, 30.4) 4.0 (0.8, 11.6) OS Median (mo) 23.8 18.7 0.79 (0.56, 1.12) K-M Estimates % (95% CI) 6 mo 91.3 (83.9, 95.4) 88.8 (80.7, 93.6) 12 mo 75.7 (66.2, 82.9) 66.3 (56.1, 74.7) 18 mo 60.0 (49.6, 68.9) 50.5 (39.9, 60.2) 24 mo 47.7 (36.6, 58.1) 38.9 (28.4, 49.3) Overall cumulative incidence of intervention for CNS disease % (95% CI) 27.9 (10.4, 48.7) 33.8 (21.5, 46.5) ORR % (95% CI) 40.7 (29.9, 52.2) 32.1 (22.4, 43.2) CBR % (95% CI) 51.9 (40.5, 63.1) 40.5 (29.9, 51.7) DOR Median (mo) 11.1 4.2 0.26 (0.12, 0.52)
The efficacy of N+C in Asian pts was consistent with that of the overall study population. No new safety signal was noted.
NCT01808573.
Medical writing assistance for this abstract was provided by Yi-Hsuan Chung, MS, of Health Care Asia Co., Ltd and funded by CANbridge Pharma Inc.
Puma Biotechnology Inc.
Puma Biotechnology Inc.
N. Masuda: Honoraria (self), Research grant/Funding (self): Chugai; AstraZeneca; Pfizer; Eli-Lilly; Eisai; Honoraria (self): Takeda; Research grant/Funding (self): Kyowa-Kirin; MSD; Novartis; Nihon-Kayaku; Daiichi Sankyo. A. Kwong: Research grant/Funding (institution): AstraZeneca; Novartis; Roche; GSK; Puma; Pfizer; IceCure; Stryker. Y.S. Yap: Honoraria (self): Novartis; Pfizer; Lilly; Eisai; MSD; AstraZeneca. S. Ow: Honoraria (self): AstraZeneca; Pfizer; Novartis; Eli Lilly. K.S. Lee: Honoraria (self): Articulate Science LLC; Advisory/Consultancy: Roche; Eli Lilly; Novartis. S.B. Kim: Advisory/Consultancy, Research grant/Funding (self): Novartis; Research grant/Funding (self): Sanofi-Aventis; Kyowa-Kirin Inc; DongKook Pharm Co.; Advisory/Consultancy: AstraZeneca; Lilly; Enzychem; Dae Hwa Pharmaceutical Co. Ltd.; ISU Abxis; Daiichi-Sankyo. H.C. Chung: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Research grant/Funding (institution): GSK; Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck-Serono; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Taiho; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Beigene; Research grant/Funding (institution): Incyte; Advisory/Consultancy: Celltrion; Advisory/Consultancy: Gloria; Advisory/Consultancy: Zymework. K. Keyvanjah; J. Bebchuk: Shareholder/Stockholder/Stock options, Full/Part-time employment: Puma Biotechnology Inc.. M-C.J. Chen: Full/Part-time employment: CANbridge Pharmaceuticals Inc.. All other authors have declared no conflicts of interest.