Cancer Res Treat.  2025 Apr;57(2):434-442. 10.4143/crt.2024.340.

Combination Therapy of Pyrotinib and Metronomic Vinorelbine in HER2+ Advanced Breast Cancer after Trastuzumab Failure (PROVE): A Prospective Phase 2 Study

• Hao C
• Wang X
• Shi Y
• Tong Z
• Li S
• Liu X
• Zhang L
• Zhang J
• Meng W
• Zhang L

• KMID: 2566862
• DOI: http://doi.org/10.4143/crt.2024.340

Abstract

Purpose
Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients.
Materials and Methods
In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.
Results
From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs.
Conclusion
Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Keyword

Pyrotinib; Metronomic vinorelbine; Trastuzumab resistance; Advanced breast cancer

Figure

• 

  Fig. 1. Kaplan-Meier curves of progression-free survival (PFS) for human epidermal growth factor receptor 2–positive advanced breast cancer patients. (A) PFS curve for entire cohort (n=36). (B) PFS for subgroups with or without lung metastasis (median, 14.3 vs. 7.6 months; nominal p=0.037). (C) PFS for subgroups primarily or secondarily resistant to trastuzumab (median, 19.7 vs. 10.9 months; nominal p=0.207). (D) PFS for subgroups previously treated with trastuzumab (median, 13.6 months) in advanced or early disease stages (median, 13.9 vs. 11.8 months). (E) PFS for subgroups with or without previous lapatinib treatment (median, 8.3 vs. 15.3 months; nominal p=0.008).

Reference

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