Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2+ Metastatic
 

Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Tria


J Clin Oncol
. 2020 Jul 17;JCO2000147. doi: 10.1200/JCO.20.00147. Online ahead of print.
Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial

Cristina Saura 1 , Mafalda Oliveira 1 , Yin-Hsun Feng 2 , Ming-Shen Dai 2 , Shang-Wen Chen 2 , Sara A Hurvitz 3 , Sung-Bae Kim 4 , Beverly Moy 5 , Suzette Delaloge 6 , William Gradishar 7 , Norikazu Masuda 8 , Marketa Palacova 9 , Maureen E Trudeau 10 , Johanna Mattson 11 , Yoon Sim Yap 12 , Ming-Feng Hou 13 , Michelino De Laurentiis 14 , Yu-Min Yeh 15 , Hong-Tai Chang 16 , Thomas Yau 17 , Hans Wildiers 18 19 , Barbara Haley 20 , Daniele Fagnani 21 , Yen-Shen Lu 22 , John Crown 23 , Johnson Lin 24 , Masato Takahashi 25 , Toshimi Takano 26 , Miki Yamaguchi 27 , Takaaki Fujii 28 , Bin Yao 29 , Judith Bebchuk 29 , Kiana Keyvanjah 29 , Richard Bryce 29 , Adam Brufsky 30 , NALA Investigators
Affiliations expand
PMID: 32678716 DOI: 10.1200/JCO.20.00147
Abstract

Purpose: NALA (ClinicalTrials.gov identifier: NCT01808573) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens.

Methods: Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m2 twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m2 twice a day 14 d/21 d). Coprimary end points were centrally confirmed progression-free survival (PFS) and overall survival (OS). NALA was considered positive if either primary end point was met (α split between end points). Secondary end points were time to CNS disease intervention, investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate, safety, and health-related quality of life (HRQoL).

Results: A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314). Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified log-rank P = .0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07; P = .2098). Fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8% v 29.2%; P = .043). ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4; P = .1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 to 0.74; P = .004). The most common all-grade adverse events were diarrhea (N+C 83% v L+C 66%) and nausea (53% v 42%). Discontinuation rates and HRQoL were similar between groups.

Conclusion: N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed.