Apatinib and trastuzumab-based chemotherapy for heavily treated primary trastuzumab-resistant metastatic breast cancer.

Background: The low incidence and poor prognosis primary trastuzumab resistance (PTR) in HER2-positive breast cancer has limited research into possible treatments. Thus, it remains unclear whether this group of patients could benefit from nontargeting HER2 antiangiogenic therapy.

Patients and methods: We collected the medical data for HER2-positive patients with PTR who received apatinib 250 mg and trastuzumab-based chemotherapy (ATBC) between March 18, 2017, and March 31, 2022. All patients had progressed on ≥2 anti-HER2 treatments, including trastuzumab and small molecular tyrosine kinase inhibitors. We evaluated tumor response and safety profiles to ATBC over a median follow-up time of 34.5 months.

Results: A total of 198 consecutively HER2-positive metastatic breast cancer patients were reviewed; 20 were PTR and received ATBC. The clinical benefit rate of the total cohort was 55.0%. No patient showed a complete response. The median PFS and overall survival (OS) of the entire cohort was 5.7 months (95% CI 2.9-8.5) and 24.6 months (95% CI 6.9-42.4), respectively. The estimated 2-year survival rate was 46.7% (95% CI 38.4-81.6%). The most common nonhematologic adverse events were hypertension (70.0%), hand-foot skin reaction (55.0%), proteinuria (40.0%), and cardiovascular decrease of LVEF (20.0%). No new toxicities were observed.

Conclusion: ATBC had favorable effects for PTR breast cancer patients in later line treatment. The toxicity of the triple-combination regimen was tolerable; thus, further research should focus on identifying PTR patients who could benefit from ATBC.