BACKGROUND: In the phase III, open-label, randomised HannaH study, fixed-dose neoadjuvant-adjuvant subcutaneous trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer was non-inferior to standard weight-based intravenous infusion in terms of serum trough concentration and pathological complete response (pCR). Evidence suggests that pCR, particularly total pCR (tpCR), is likely to predict clinical benefit. We report associations between tpCR and event-free survival (EFS) from HannaH (the largest population from a single study of patients presenting with newly diagnosed HER2-positive breast cancer treated with neoadjuvant-adjuvant trastuzumab to date) plus long-term efficacy and safety. METHODS: Eligible patients received four cycles of neoadjuvant docetaxel followed by four cycles of fluorouracil/epirubicin/cyclophosphamide administered concurrently with 3-weekly subcutaneous (600 mg fixed dose) or intravenous trastuzumab (8 mg/kg loading, 6 mg/kg maintenance doses). Post-surgery, patients received adjuvant trastuzumab as randomised to complete 1 year of standard treatment. In exploratory analyses, we used Cox regression to assess associations between tpCR and EFS. EFS rates per subgroup were estimated using the Kaplan-Meier method. FINDINGS: Three-year EFS rates were 76% for subcutaneous and 73% for intravenous trastuzumab (unstratified hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.69-1.30; intention-to-treat population). Three-year overall survival rates were 92% for subcutaneous and 90% for intravenous trastuzumab (unstratified HR 0.76, 95% CI 0.44-1.32). tpCR was associated with a reduced risk of an EFS event: subcutaneous arm HR 0.38 (95% CI 0.22-0.65); intravenous arm HR 0.32 (95% CI 0.18-0.60). Results were similar for subgroups, including oestrogen receptor status. The few additional adverse events occurring during treatment-free follow-up were balanced between arms. INTERPRETATION: Long-term efficacy supports the established non-inferiority of subcutaneous trastuzumab, and its safety profile remains consistent with the known intravenous profile. In each of HannaH's treatment arms, tpCR was associated with improved EFS, adding to evidence that tpCR is associated with clinical benefit in HER2-positive early breast cancer.

Asan Medical Center University of Ulsan College of Medicine Department of Oncology 88 Olympic ro 43 gil Songpa gu Seoul South Korea

Chang Gung Memorial Hospital Department of Surgery No 123 Dinghu Rd Guishan District Taoyuan Taiwan

Changhua Christian Hospital No 135 Nanhsiao St Changhua City Changhua County Taiwan

CHU Jean Minjoz Chemotherapy Oncology 3 Boulevard Alexandre Fleming 25030 Besançon France

City Clinical Oncology Hospital 62 Chemotherapeutic Department Moscow 143423 Russia

F Hoffmann La Roche Ltd Grenzacherstrasse 124 4070 Basel Switzerland

Genentech Inc Global Pharma Development 1 DNA Way South San Francisco CA 94080 USA

Hospital Nacional Edgardo Rebagliati Martins Av Rebagliati 490 Jesús María Lima 11 Peru

Hospital Pérola Byington and FMUSP Department of Gynecology and Obstetrics Avenida Brigadeiro Luís Antônio 683 Bela Vista São Paulo SP 01317 000 Brazil

NN Blokhin Cancer Research Center Russian Academy of Medical Sciences Kashirskoye Shosse 24 115478 Moscow Russia

Palacký University Medical School and Teaching Hospital Department of Oncology 1 P Pavlova 185 6 779 00 Olomouc Czech Republic

Samsung Medical Center Sungkyunkwan University School of Medicine Department of Medicine 81 Irwon ro Gangnam gu Seoul South Korea

Sana Klinikum Offenbach GmbH Department of Obstetrics and Gynecology and Breast Cancer and Gynecology Cancer Center Starkenburgring 66 D 63069 Offenbach Germany

St Johannes Hospital Johannesstraße 9 13 44137 Dortmund Germany

St John's Cancer Center 20 090 Lublin Poland

Citace poskytuje Crossref.org

Subcutaneous vs Intravenous Trastuzumab for Patients With ERBB2-Positive Early Breast Cancer: Final Analysis of the HannaH Phase 3 Randomized Clinical Trial