Overall Survival With Pyrotinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic...

Phase II and III trials have demonstrated progression-free survival (PFS) benefits of pyrotinib plus capecitabine over lapatinib plus capecitabine in HER2-positive metastatic breast cancer (MBC). However, long-term overall survival (OS) data from a single-center cohort remain limited. This pooled analysis compared OS between the two regimens and explored outcomes across prespecified subgroups.

We included patients with HER2-positive MBC from our center enrolled in a Phase Ic study, a Phase II study, or the Phase III PHOEBE trial. The primary endpoint was OS. OS was analyzed using Kaplan-Meier estimates, log-rank tests, and a multivariable Cox model adjusted for ECOG performance status, pathological grade, prior anti-HER2 therapy, trastuzumab exposure duration, trastuzumab resistance, and prior chemotherapy lines. The proportional hazards assumption was assessed using Schoenfeld residuals. Exploratory subgroup analyses used prespecified categories.

At data cutoff, 82 patients were included; 53 received pyrotinib plus capecitabine and 29 received lapatinib plus capecitabine. Baseline characteristics were comparable between groups. Median OS was 74.61 months (95% CI 41.10-not reached) with pyrotinib plus capecitabine and 30.98 months (26.12-50.76) with lapatinib plus capecitabine (log-rank p = 0.0053). Cox models suggested a reduced risk of death with pyrotinib plus capecitabine. Subgroup analyses were exploratory and should be interpreted cautiously because several subgroup estimates were imprecise.

In this single-center pooled analysis, pyrotinib plus capecitabine was associated with significantly longer OS than lapatinib plus capecitabine in patients with HER2-positive MBC. These exploratory results are consistent with prior Phase II/III trials and provide evidence supporting the OS benefit of pyrotinib.