P Conte1, A Frassoldati2, G Bisagni3, A A Brandes4, M Donadio5, O Garrone6, F Piacentini7, L Cavanna8, F Giotta9, M Aieta10, V Gebbia11, A Molino12, A Musolino13, A Ferro14, R Maltoni15, S Danese16, C Zamagni17, A Rimanti18, K Cagossi19, A Russo20, P Pronzato21, F Giovanardi3, G Moretti3, L Lombardo4, A Schirone2, A Beano5, L Amaducci22, E A Bajardi11, R Vicini23, S Balduzzi23, R D'Amico24, V Guarneri25. 1. Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; Medical Oncology 2, Istituto Oncologico Veneto (IOV), IRCCS, Padova, Italy. Electronic address: pierfranco.conte@unipd.it. 2. Clinical Oncology, Department of Morphology, Surgery and Experimental Medicine, S Anna University Hospital, Ferrara, Italy. 3. Department of Oncology and Advanced Technologies, Oncology Unit, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. 4. Medical Oncology, Azienda Unità Sanitaria Locale di Bologna-IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy. 5. Department of Medical Oncology 1, Città della Salute e della Scienza Hospital, Turin, Italy. 6. Medical Oncology, A.O. S. Croce and Carle Teaching Hospital, Cuneo, Italy. 7. Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, Modena, Italy; Azienda Ospedaliero-Universitaria di Modena, Modena, Italy. 8. Department of Oncology-Hematology, G. da Saliceto Hospital, Piacenza, Italy. 9. Division of Medical Oncology, IRCCS, Giovanni Paolo II Hospital, Bari, Italy. 10. Division of Medical Oncology, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero Vulture (PZ), Italy. 11. Medical Oncology, Casa di Cura La Maddalena, University of Palermo, Palermo, Italy. 12. Oncology Unit, Verona University Hospital, Verona, Italy. 13. Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 14. Medical Oncology, Santa Chiara Hospital, Trento, Italy. 15. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRST, IRCCS, Meldola, Italy. 16. Department of Gynecology and Obstetrics, Ospedale S. Anna, Turin, Italy. 17. Policlinico S.Orsola-Malpighi, SSD Oncologia Medica Addarii, Bologna, Italy. 18. Medical Oncology, Azienda Ospedaliera Carlo Poma, Mantova, Italy. 19. Division of Medical Oncology, "B.Ramazzini" Hospital, Carpi, Italy. 20. Section of Medical Oncology, Department of Surgical and Oncological Sciences, University of Palermo, Palermo, Italy. 21. Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino-IST, Genova, Italy. 22. Medical Oncology Unit, Ospedale degli Infermi Faenza, Faenza, Italy. 23. Department of Diagnostic and Clinical Medicine and Public Health, Statistics Unit, University Hospital of Modena and Reggio Emilia, Modena, Italy. 24. Azienda Ospedaliero-Universitaria di Modena, Modena, Italy; Department of Diagnostic and Clinical Medicine and Public Health, Statistics Unit, University Hospital of Modena and Reggio Emilia, Modena, Italy. 25. Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; Medical Oncology 2, Istituto Oncologico Veneto (IOV), IRCCS, Padova, Italy.
Abstract
Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age ≤35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR) <1.29 was chosen as the non-inferiority margin. Analyses according to the frequentist and Bayesian approach were planned. Secondary end points included 2-year failure rate and cardiac safety. Results: A total of 1254 patients from 82 centers were randomized (arm A, long: n = 627; arm B, short: n = 626). Five-year DFS is 88% in the long and 85% in the short arm. The HR is 1.13 (90% CI 0.89-1.42), with the upper limit of the CI crossing the non-inferiority margin. According to the Bayesian analysis, the probability that the short arm is non-inferior to the long one is 80%. The 5-year overall survival (OS) is 95.2% in the long and 95.0% in the short arm (HR 1.07, 90% CI 0.74-1.56). Cardiac events are significantly lower in the short arm (risk-ratio 0.33, 95% CI 0.22-0.50, P < 0.0001). Conclusions: This study failed to show the non-inferiority of a shorter trastuzumab administration. One-year trastuzumab remains the standard. However, a 9-week administration decreases the risk of severe cardiac toxicity and can be an option for patients with cardiac events during treatment and for those with a low risk of relapse. Trial Registration: EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.
RCT Entities:
Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancerpatients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age ≤35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR) <1.29 was chosen as the non-inferiority margin. Analyses according to the frequentist and Bayesian approach were planned. Secondary end points included 2-year failure rate and cardiac safety. Results: A total of 1254 patients from 82 centers were randomized (arm A, long: n = 627; arm B, short: n = 626). Five-year DFS is 88% in the long and 85% in the short arm. The HR is 1.13 (90% CI 0.89-1.42), with the upper limit of the CI crossing the non-inferiority margin. According to the Bayesian analysis, the probability that the short arm is non-inferior to the long one is 80%. The 5-year overall survival (OS) is 95.2% in the long and 95.0% in the short arm (HR 1.07, 90% CI 0.74-1.56). Cardiac events are significantly lower in the short arm (risk-ratio 0.33, 95% CI 0.22-0.50, P < 0.0001). Conclusions: This study failed to show the non-inferiority of a shorter trastuzumab administration. One-year trastuzumab remains the standard. However, a 9-week administration decreases the risk of severe cardiac toxicity and can be an option for patients with cardiac events during treatment and for those with a low risk of relapse. Trial Registration: EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.
Authors: Helena Earl; Louise Hiller; Anne-Laure Vallier; Shrushma Loi; Karen McAdam; Luke Hughes-Davies; Daniel Rea; Donna Howe; Kerry Raynes; Helen B Higgins; Maggie Wilcox; Chris Plummer; Betania Mahler-Araujo; Elena Provenzano; Anita Chhabra; Sophie Gasson; Claire Balmer; Jean E Abraham; Carlos Caldas; Peter Hall; Bethany Shinkins; Christopher McCabe; Claire Hulme; David Miles; Andrew M Wardley; David A Cameron; Janet A Dunn Journal: Health Technol Assess Date: 2020-08 Impact factor: 4.014
Authors: Aleix Prat; Valentina Guarneri; Laia Paré; Gaia Griguolo; Tomás Pascual; Maria V Dieci; Núria Chic; Blanca González-Farré; Antonio Frassoldati; Esther Sanfeliu; Juan M Cejalvo; Montserrat Muñoz; Giancarlo Bisagni; Fara Brasó-Maristany; Loredana Urso; Maria Vidal; Alba A Brandes; Barbara Adamo; Antonino Musolino; Federica Miglietta; Benedetta Conte; Mafalda Oliveira; Cristina Saura; Sònia Pernas; Jesús Alarcón; Antonio Llombart-Cussac; Javier Cortés; Luis Manso; Rafael López; Eva Ciruelos; Francesco Schettini; Patricia Villagrasa; Lisa A Carey; Charles M Perou; Federico Piacentini; Roberto D'Amico; Enrico Tagliafico; Joel S Parker; Pierfranco Conte Journal: Lancet Oncol Date: 2020-11 Impact factor: 41.316