A combination of pyrotinib and metronomic vinorelbine has demonstrated promising efficacy and a manageable safety profile in patients with HER2-positive advanced breast cancer who have previously been treated with trastuzumab. The findings come from a single-center, prospective phase 2 trial conducted in China, offering a potential treatment option in settings where HER2-targeted antibody-drug conjugates (ADCs) are not readily available due to economic or accessibility factors.
The study, published in Cancer Research and Treatment, enrolled 36 patients and reported a median progression-free survival (PFS) of 13.5 months (95% CI, 8.33-18.5) with the pyrotinib plus vinorelbine regimen. The overall response rate (ORR) was 38.9% (95% CI, 23.1%-56.5%), including 14 partial responses, and the disease control rate (DCR) reached 83.3% (95% CI, 67.2%-93.6%).
Study Design and Patient Population
The open-label phase 2 study included patients aged 18 to 75 years with histologically confirmed HER2-positive recurrent or metastatic breast cancer who had experienced disease progression on trastuzumab or within 12 months of completing treatment. All patients received pyrotinib at 400 mg once daily plus vinorelbine at 40 mg thrice weekly in 21-day cycles until disease progression, unacceptable toxicity, or patient withdrawal.
The primary endpoint was PFS, with a target of extending the median PFS to 12.0 months, based on a historical control of 6.4 months from the EMILIA trial using lapatinib and capecitabine. Secondary endpoints included ORR, duration of response, DCR, overall survival (OS), and safety.
The median age of the enrolled patients was 54 years (range, 31-71), with the vast majority (97.2%) being female. Metastatic sites at baseline included lung (75.0%), liver (33.3%), bone (50.0%), brain (16.7%), and skin, lymph nodes, and soft tissue (88.9%). A significant proportion of patients (52.8%) had hormone receptor–positive disease.
Efficacy Outcomes
Subgroup analysis revealed that patients with lung metastases (n = 27) had a median PFS of 14.2 months, compared to 7.6 months for those without lung metastases (n = 9; nominal P = .037). Patients with primary trastuzumab resistance (n = 9) achieved a median PFS of 19.7 months versus 10.9 months for those with secondary resistance (n = 27; nominal P = .207). Those previously treated with lapatinib (n = 15) had a median PFS of 8.3 months compared to 15.3 months for those naive to lapatinib (n = 21; nominal P = .008).
Safety Profile
The combination therapy was generally well-tolerated. The most common adverse events (AEs) of any grade included diarrhea (94.4%), nausea (80.6%), and vomiting (75.0%). Grade 3 AEs, reported in 17 patients, consisted of diarrhea (27.8%), vomiting (8.3%), and stomachache (5.6%). No grade 4 or 5 AEs were observed, and no patient deaths were attributed to treatment-related AEs.
Clinical Implications
"Anti-HER2 antibody-drug conjugates are currently the preferred regimen for patients previously treated with trastuzumab…However, their use is not yet common practice due to economic factors. As such, exploration of small molecule combination therapies is still necessary," wrote lead study author Chunfang Hao, MD, PhD, of the Department of Breast Oncology at Tianjin Medical University Cancer Institute and Hospital in China, and colleagues.
The study authors acknowledged limitations, including the single-arm design and small sample size. They also noted that the lack of prior treatment with ADCs like ado-trastuzumab emtansine and fam-trastuzumab deruxtecan-nxki in their patient population, due to limited availability and economic factors, impacts the extrapolation of the results to a global population. Despite these limitations, the researchers concluded that the dual-oral regimen of pyrotinib and vinorelbine appears to be a feasible approach in this setting and warrants further study in larger randomized trials.
