NALA
In HER2-positive metastatic breast cancer after ≥2 anti-HER2 regimens, does neratinib–capecitabine improve outcomes versus lapatinib–capecitabine?
Trial design and population
621 patients with HER2-positive metastatic breast cancer after ≥2 prior anti-HER2 regimens in metastatic setting.
Neratinib 240 mg orally daily plus capecitabine 750 mg/m² twice daily days 1–14 every 21 days vs lapatinib 1,250 mg daily plus capecitabine 1,000 mg/m² twice daily days 1–14.
621
PFS and OS
Key results
Median PFS was 8.8 vs 6.6 months (HR 0.76, 95% CI 0.63–0.93; P=.0059); 12-month PFS was 29% vs 15%. Median OS was 24.0 vs 22.2 months (HR 0.88, 95% CI 0.72–1.07; P=.2086). CNS intervention was less frequent with neratinib (22.8% vs 29.2%).
Source-reported outcome visualization
12-month progression-free survival · 12 months
Source-reported endpoint and unit; median survival is not converted into an NNT.
Absolute Effect
Absolute 12-month PFS difference 14 points; NNT 8 based on being progression-free at 12 months. OS improvement was not statistically significant.
NNT: 8 based on 12-month PFS. Endpoint/time horizon are stated above; do not convert median survival differences into NNT.
NNH: Not quantifiable. Grade 3 diarrhoea occurred in approximately 24% with neratinib despite protocol prophylaxis; capecitabine adds hand-foot syndrome and diarrhoea. Prophylactic antidiarrhoeal management is important.
Safety and treatment burden
Grade 3 diarrhoea occurred in approximately 24% with neratinib despite protocol prophylaxis; capecitabine adds hand-foot syndrome and diarrhoea. Prophylactic antidiarrhoeal management is important.
Follow-up, maturity and limitations
Primary PFS and updated OS analyses.
Comparator is historical; modern HER2-directed sequences differ. The modest median PFS difference and absence of significant OS benefit must be considered.
Clinical interpretation
Current-practice context · reviewed 20 October 2026
Historical evidence is separated from current sequencing. Confirm local regulatory status, current guidelines, biomarkers, prior therapies and patient-specific contraindications before applying these results. Newer treatments may have changed the preferred sequence; where NNT/NNH cannot be defensibly quantified, no surrogate calculation is made.