Early results of neoadjuvant therapy with pyrotinib, subcutaneous trastuzumab, and capecitabine for HER2-positive early breast cancer from a prospective, single-arm, multicenter trial.

Abstract

606 Background: Neoadjuvant therapy has become a standard approach for HER2-positive early breast cancer, improving outcomes, pCR, and survival. Prior studies show pyrotinib combined with trastuzumab and chemo is effective and safe, but mainly via intravenous routes, impacting quality of life. This trial is the first to assess a fully oral regimen—pyrotinib, SC trastuzumab, and capecitabine—in low- to intermediate-risk patients, focusing on efficacy and safety. Methods: This single-arm, multicenter phase II trial (NCT06483386) will enroll 109 treatment-naïve adults with stage I-II, T1c-2N0-1 HER2-positive EBC (IHC 3+ or IHC 2+/FISH+). From May 2024 to June 2026, patients will receive 6 cycles of neoadjuvant pyrotinib (400mg daily), SC trastuzumab (600mg q3w), and capecitabine (1000mg/m² BID, days 1-14 followed by a 7-day break). The primary endpoint is pathological complete response (pCR) rate, as defined by RECIST 1.1. Secondary endpoints include event-free survival (EFS), objective response rate (ORR), breast-conserving rate (BCR) and safety. Results: A total of 47 patients were enrolled from May 2024 to December 2025, of whom 43 underwent surgery and 43 had pathologic assessment available. The median age was 51 years (range 33-65), and 97.9% had an ECOG PS of 0. The majority of patients had stage II disease (89.4%), with T2 tumors (91.5%); 57.4% were clinically node-positive. The pCR rate among pts with evaluable pathology was 48.8% (21/43), and ORR was over 90%. The BCR was 65.1% (25/48). In biomarker-defined subgroups, total pathological complete response (tpCR) was achieved in 53.6% (15/28) of ER negative, HER2 positive patients, and in 40.0% (6/15) of ER positive, HER2 positive patients. The most common AEs were diarrhea, nausea, anorexia, and gastrointestinal dysfunction. The incidence of grade 3 diarrhea is 19.1%, and all cases are controllable with medication, confirming good safety profile. Conclusions: The fully non-intravenous neoadjuvant regimen combining pyrotinib, SC trastuzumab, and capecitabine is an efficacious and safe regimen for patients with low- to intermediate-risk HER2-positive early breast cancer. This regimen offers a more convenient and less burdensome treatment for this patient population, potentially improving quality of life and treatment adherence. Clinical trial information: NCT06483386 .