Christian Jackisch1, Roberto Hegg2, Daniil Stroyakovskiy3, Jin-Seok Ahn4, Bohuslav Melichar5, Shin-Cheh Chen6, Sung-Bae Kim7, Mikhail Lichinitser8, Elżbieta Starosławska9, Georg Kunz10, Silvia Falcon11, Shou-Tung Chen12, Aulde Crepelle-Fléchais13, Dominik Heinzmann13, Mona Shing14, Xavier Pivot15. 1. Sana Klinikum Offenbach GmbH, Department of Obstetrics and Gynecology & Breast Cancer and Gynecology Cancer Center, Starkenburgring 66, D-63069, Offenbach, Germany. Electronic address: christian.jackisch@sana.de. 2. Hospital Pérola Byington and FMUSP, Department of Gynecology and Obstetrics, Avenida Brigadeiro Luís Antônio, 683 - Bela Vista, São Paulo - SP, 01317-000, Brazil. 3. City Clinical Oncology Hospital 62, Chemotherapeutic Department, Moscow, 143423, Russia. 4. Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, South Korea. 5. Palacký University Medical School & Teaching Hospital, Department of Oncology, I. P. Pavlova 185/6, 779 00, Olomouc, Czech Republic. 6. Chang Gung Memorial Hospital, Department of Surgery, No. 123, Dinghu Rd, Guishan District, Taoyuan, Taiwan. 7. Asan Medical Center, University of Ulsan College of Medicine, Department of Oncology, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, South Korea. 8. NN Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoye Shosse 24, 115478, Moscow, Russia. 9. St. John's Cancer Center, 20-090, Lublin, Poland. 10. St. Johannes Hospital, Johannesstraße 9-13, 44137, Dortmund, Germany. 11. Hospital Nacional Edgardo Rebagliati Martins, Av. Rebagliati 490, Jesús María, Lima 11, Peru. 12. Changhua Christian Hospital, No. 135, Nanhsiao St, Changhua City, Changhua County, Taiwan. 13. F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland. 14. Genentech, Inc., Global Pharma Development, 1 DNA Way, South San Francisco, CA, 94080, USA. 15. CHU Jean Minjoz, Chemotherapy - Oncology, 3 Boulevard Alexandre Fleming, 25030, Besançon, France.
Abstract
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 withneoadjuvant-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.
RCT Entities:
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.
Authors: S Dent; C Ammendolea; A Christofides; S Edwards; D Incekol; B Pourmirza; S Kfoury; B Poirier Journal: Curr Oncol Date: 2019-02-01 Impact factor: 3.677
Authors: S Di Cosimo; C Campbell; H A Azim; G Galli; G Bregni; G Curigliano; C Criscitiello; M Izquierdo; L de la Pena; D Fumagalli; L Fein; J Vinholes; W M J Ng; M Colleoni; A Ferro; B J Naume; A Patel; J Huober; M J Piccart-Gebhart; J Baselga; E de Azambuja Journal: Eur J Cancer Date: 2017-12-08 Impact factor: 9.162
Authors: Sherko Kuemmel; Carlo A Tondini; Jacinta Abraham; Zbigniew Nowecki; Bartosz Itrych; Erika Hitre; Bogusława Karaszewska; Alejandro Juárez-Ramiro; Flavia Morales-Vásquez; Jose Manuel Pérez-García; Servando Cardona-Huerta; Estefania Monturus; Marco Sequi; Eleonora Restuccia; Mark Benyunes; Miguel Martín Journal: Breast Cancer Res Treat Date: 2021-03-21 Impact factor: 4.872