Pertuzumab Vs. Pyrotinib in Combination With Trastuzumab and Taxanes for First-Line Treatment of HER2+ MBC: A...

Taxanes combined with trastuzumab plus either pertuzumab (THP) or pyrotinib (THPy) are standard first-line treatments for HER2-positive metastatic breast cancer (HER2+ MBC). Nevertheless, direct comparative evidence remains insufficient. This study compared the efficacy and safety of THP vs. THPy for HER2+ MBC.

The multicenter retrospective study comprised patients treated in first-line with either THP or THPy from January 2018 to March 2025. Confounding factors were adjusted using 1:1 propensity score matching (PSM) and multivariable Cox regression. Progression-free survival (PFS) was the primary endpoint, with clinical benefit rate (CBR), objective response rate (ORR), and safety as secondary endpoints.

A total of 411 patients were enrolled (THP: 148; THPy: 263). After matching, 139 pairs formed. Before PSM, patients in the THPy group experienced a longer median PFS than those in the THP group (23.6 vs. 19.3 months, HR = 0.72, 95% CI: 0.53-0.97, p = 0.031). After PSM, THPy still provided a PFS benefit (23.6 vs. 17.3 months, HR = 0.68, 95% CI: 0.48-0.97, p = 0.033), with an adjusted HR of 0.44 (95% CI 0.30-0.66, p < 0.001). Before PSM, the THPy group had a lower ORR than the THP group (69.2% vs. 81.1%, p = 0.009), but after PSM, this disparity in ORR was no longer significant (74.1% vs. 79.9%, p = 0.254), and CBR remained comparable between the two groups throughout. THPy showed potential PFS benefit in the subgroup with de novo stage IV disease and liver metastasis. Gastrointestinal toxicities were more common in the THPy group, with diarrhea being the most prominent (any grade: 76.1%; grade ≥ 3: 22.7%).

THPy may provide PFS benefit over THP in HER2+ MBC, with suggestive advantages in patients with de novo stage IV disease and liver metastasis. A higher frequency of diarrhea and other gastrointestinal toxicities was observed in the THPy regimen.