Abstract
IMPORTANCE: THP (trastuzumab + paclitaxel + pertuzumab) and THPy (trastuzumab + paclitaxel + pyrotinib) are widely used as first-line regimens for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) in China. However, direct comparative data on their efficacy and safety remain scarce. OBJECTIVE: To evaluate and compare the clinical outcomes of THPy and THP in the first-line treatment of HER2-positive MBC to guide clinical decision-making. DESIGN: Real-world, multicenter retrospective study conducted from 2020 to 2024. SETTING: Five large breast cancer centers in China. PARTICIPANTS: A total of 145 patients with HER2-positive MBC were included before propensity score matching (PSM). After PSM, 76 patients (38 in each group) were analyzed. INTERVENTION(S) OR EXPOSURE(S): Patients received either THP (trastuzumab + paclitaxel + pertuzumab) or THPy (trastuzumab + paclitaxel + pyrotinib) as first-line treatment. MAIN OUTCOME(S) AND MEASURE(S): The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate, and safety profile. RESULTS: Before PSM, 145 patients were included, with the median follow-up of 9.4 months. The ORR was significantly higher in the THPy group (75.0%) compared to the THP group (56.8%; P = .023). Median PFS showed a trend favoring THPy (19.80 months vs 15.57 months; Log-rank P = .343). After PSM, 76 patients were matched, with the median PFS of 24.33 months versus 14.50 months for THPy and THP groups, respectively. Though the difference in PFS was not statistically significant (Log-rank P = .309), THPy demonstrated a higher ORR compared to THP (78.9% vs 57.9%; P = .048). Further subgroup analysis revealed greater benefits of THPy, particularly in patients with prior neoadjuvant therapy (hazard ratio [HR] = 0.261; 95% CI: 0.072-0.940). Regarding safety, THPy was associated with a higher incidence of grade 3/4 diarrhea (26.6% vs 3.1%) as well as increased rates of neutropenia, anemia, alanine aminotransferase elevation, fatigue, and peripheral neuropathy compared to THP. CONCLUSION AND RELEVANCE: Both THP and THPy are effective first-line options for HER2-positive MBC. While THPy demonstrates a higher ORR and a trend toward longer PFS, it also carries a higher incidence of adverse events, particularly diarrhea. These findings offer preliminary insights that may help inform treatment decisions, pending further validation in prospective studies.