Neoadjuvant trastuzumab in a sequential nonanthracycline-based regimen for patients with stage II-III breast cancer

Abstract

e11559 Background: Recently, some studies have demonstrated benefit from adding trastuzumab to neoadjuvant anthracycline-containing chemotherapy for HER2-positive breast cancer patients. However, trastuzumab can increase cardiotoxicity, particularly when combined with anthracyclines. This represents a relevant issue for patients who usually need to receive radiotherapy or further systemic treatment. Methods: In the late 2007 we started a phase II study for testing activity and safety of neoadjuvant trastuzumab in association with sequential chemotherapy, based on favourable in vitro combination index, proven efficacy, and moderate cardiotoxicity. Weekly trastuzumab for 18 weeks was combined with cisplatin 80 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1+8 q3w for 3 courses, followed by docetaxel 100 mg/m2 q3w for further 3 courses. Peg- filgrastim was administered to prevent neutropenia. Adjuvant trastuzumab q3w was planned for one year. Eligible patients had stage II-III core-biopsied breast carcinoma with overexpressed or amplified HER2/neu. Adequate cardiac function with LVEF ≥ 50% was required for trastuzumab administration. Primary end-point was pathologic complete responses (pCR) rate. The study is registered on the European Clinical Trials Database. Results: Among 17 enrolled patients, 15 were evaluable for primary end-point. Median age was 50 years (range 23–70), stage II and III breast cancer in 4 and 13 patients, respectively, with 4 cases of stage IIIB (2 T4b and 2 T4d), and 2 women with synchronous bilateral cancer. Neoadjuvant regimen yielded 6/15 pCR (40%). Only 3/12 patients treated with lymphadenectomy due to initial clinically suspected axillary nodes presented pN+, but none of them had more than 3 positive nodes. In two cases we observed a total pCR, involving both primary tumor and axillary nodes. Treatment was safe, with only 2 events of short G4 non febrile neutropenia on 97 chemotherapy cycles. Alopecia was moderate at the end of treatment, without any case of complete hair loss. No significant cardiac dysfunction was recorded during the neoadjuvant therapy. Conclusions: The present sequential non anthracycline-based chemotherapy associated with weekly trastuzumab showed promising results in neoadjuvant setting. No significant financial relationships to disclose.