Findings from an Asian subgroup of patients with previously-treated HER2-positive metastatic breast cancer presented at the ESMO Asia Virtual Congress 2020 (20 to 22 November 2020) showed these patients achieved prolonged survival and improved responses following combination treatment with neratinib plus capecitabine, as compared to lapatinib plus capecitabine.  

Ming Shen Dai of the Department of Hematology and Oncology, Tri-Service General Hospital – Neihu Branch in Taipei City, Taiwan reported findings from the exploratory analysis of data from the pan-Asian subgroup of the multinational, randomised, open-label, phase III NALA trial (NCT01808573).

Previously reported results from NALA demonstrating significantly extended progression-free survival (PFS) and time to intervention for central nervous system (CNS) disease with neratinib/capecitabine over lapatinib/capecitabine in these patients formed the basis for the US Food and Drug Administration approval of treatment with neratinib plus capecitabine for metastatic HER2-positive breast cancer.

In NALA, patients with centrally confirmed HER2-positive metastatic breast cancer who had received ≥2 prior HER2-directed regimens were randomised equally to  treatment with neratinib at 240 mg daily  plus capecitabine at 750 mg/m2 twice daily on days 1-14 or to receive lapatinib at 1250 mg daily plus capecitabine at 1000 mg/m2 twice daily on days 1-14 in 21-day cycles.

The co-primary endpoints of the study included centrally confirmed PFS and overall survival (OS), while secondary endpoints included intervention for CNS disease, objective response rate (ORR), duration of response (DoR), clinical benefit rate (CBR), and safety.

Neratinib significantly improved all investigated parametres in Asian patients

Of the 202 Asian patients within the intention-to-treat population, 129 (63.9%) were Chinese from Taiwan and Hong Kong. In the cohort of Asian patients, 104 were treated with the neratinib combination and 98 received the lapatinib combination.

Median PFS was significantly improved to 7.0 months with neratinib/capecitabine compared to 5.4 months with lapatinib/capecitabine (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.40-0.82; stratified log-rank p = 0.0021). Six-, 12-, and 18-month PFS rates with the respective treatments were 53.7% (95% CI 42.9-63.3) versus 33.8% (95% CI 23.9-43.8), 33.5% (95% CI 23.4-43.9) versus 10.0% (95% CI 4.4-18.6), and 19.9% (95% CI 11.2-30.4) versus 4.0% (95% CI 0.8-11.6).


Primary endpoint, centrally-confirmed progression-free survival: Log-rank test and Cox model showed a statistically significant difference in centrally-confirmed PFS, with an decrease in the risk of disease progression of 42% in the pan-Asian population.

© Ming Shen Dai.

Improvements in OS were also demonstrated with neratinib; median OS was 23.8 months with neratinib/capecitabine versus 18.7 months with lapatinib/cabecitabine (HR 0.80; 95% CI 0.55-1.15; stratified log-rank p = 0.2348). The 6-, 12-, 18-, and 24-month OS rates with the respective treatments were 91.3% (95% CI 83.9-95.4) versus 88.8% (95% CI 80.7-93.6), 75.7% (95% CI 66.2-82.9) versus 66.3% (95% CI 56.1-74.7), 60.0% (95% CI 49.6-68.9) versus 50.5% (95% CI 38.9-60.2), and 47.7% (95% CI 36.6-58.1) versus 38.9% (95% CI 28.4-49.3).

The overall cumulative incidence of intervention for CNS disease was lower (27.9%) with neratinib/capecitabine compared to 33.8% with lapatinib/capecitabine (p = 0.039).

Neratinib/capecitabine provided greater responses over lapatinib/capecitabine in the Asian patients; the ORRs were 40.7% versus 32.1% and the CBRs were 51.9% versus 40.5%, respectively. In responding patients, the median DoR was more than doubled with neratinib (median 11.1 months) compared to median 4.2 months with lapatinib/capcitabine.

The most frequently reported treatment-emergent adverse event was diarrhoea in 78.8% of patients reciving the neratinib regimen and 51.0% of those receiving the lapatinib combination, which were all grade ≤3. Treatment discontinuation rates due to diarrhoea occurred with neratinib in 1% of patients; no patients receiving lapatinib discontinuated due to diarrhoea.


Findings from the Asian cohort were consistent with previous reports for neratinib plus capecitabine compared with lapatinib plus capecitabine in patients with metastatic HER2-positive breast cancer, according to the study authors.

The study was sponsored by Puma Biotechnology Inc.

Editorial assistance was funded by CANbridge Pharmaceuticals Inc.


46O – Dai MS, Feng YH, Chen SW, et al. Neratinib + Capecitabine (N+C) vs Lapatinib + Capecitabine (L+C) in Asians with HER2+ Metastatic Breast Cancer (MBC) Previously Treated with Two or More HER2-Directed Regimens: A Pan-Asian Analysis of the Phase III NALA Trial. ESMO Asia Virtual Congress 2020 (20-22 November).