breast cancer

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial

In the September 20, 2020 edition of Journal of Clinical Oncology, Cristina Saura and colleagues report on the results of the NALA trial.

PURPOSE

NALA was a randomized, active-controlled, phase III trial assessing the utility of the irreversible pan-HER tyrosine kinase inhibitor neratinib, plus capecitabine (N+C) versus lapatinib plus capecitabine (L+C) in patients with centrally confirmed HER-2/neu-positive, advanced breast cancer (MBC) with at least 2 prior HER-2/neu-directed metastatic breast cancer regimens.

METHODS

Patients, including those with asymptomatic, stable CNS disease, were randomized in a 1:1 fashion to neratinib (240 mg once every day) plus capecitabine (750 mg/m2 twice a day 14 /21 days) with antidiarrheal loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m2 twice a day 14/21 days). Centrally confirmed PFS and OS were co-primary endpoints. NALA results were 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, ORR, DoR, CBR, safety, and health-related quality of life (HRQoL).

621 patients from 28 countries were randomized (N+C, n = 307; L+C, n = 314). Centrally reviewed progression free survival was improved with N+C (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 – 38.9) and L+C 26.7% (95% CI, 21.5 – 32.4; P = .1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 – 0.74; P = .0004). 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. The authors concluded “N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed.”

Reference:

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial

https://ascopubs.org/doi/full/10.1200/JCO.20.00147

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