PMID- 35487845 OWN - NLM STAT- MEDLINE DCOM- 20220628 LR - 20220716 IS - 1532-3080 (Electronic) IS - 0960-9776 (Print) IS - 0960-9776 (Linking) VI - 64 DP - 2022 Aug TI - Safety and efficacy of adjuvant subcutaneous trastuzumab in human epidermal growth factor receptor 2-positive early breast cancer: Final results of the SafeHER study. PG - 151-158 LID - S0960-9776(22)00042-X [pii] LID - 10.1016/j.breast.2022.03.001 [doi] AB - AIM: To report the final results of the 5-year follow-up of the non-randomized SafeHER Phase III study (NCT01566721) describing the safety, tolerability, and efficacy of subcutaneous (SC) trastuzumab alone and in combination with concurrent or sequential chemotherapy. METHODS: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) with no prior anti-HER2 therapy were included. SC trastuzumab was administered every 3 weeks for 18 cycles as adjuvant therapy with or without chemotherapy (concurrent or sequential). The primary objective was overall safety and tolerability of SC trastuzumab; efficacy was a secondary objective. RESULTS: No new safety signals were observed during the final evaluation. The majority of adverse events (AEs) were grade 1 or 2 across the chemotherapy subgroups. Treatment discontinuation due to AEs was 5.1% for the intent-to-treat (ITT) population and similar for all chemotherapy subgroups. The overall disease-free survival (DFS) 5-year event-free rate in the ITT population (n = 2573) was 86.6% (95% CI, 85.2%-87.9%) with a median follow-up of 72 months. Based on chemotherapy timing, the no (n = 235), concurrent (n = 1533), and sequential (n = 805) chemotherapy subgroups had DFS 5-year event-free rates (95% CI) of 88.5% (83.4%-92.2%), 88.4% (86.6%-89.9%), and 82.6 (79.7%-85.2%), respectively. CONCLUSIONS: The 5-year follow-up analysis of the SafeHER trial demonstrating that SC trastuzumab has an acceptable safety profile, including cardiac toxicity, and efficacy for the treatment of HER2-positive EBC with and without chemotherapy, corresponding with historical data with trastuzumab. CI - Copyright (c) 2022. Published by Elsevier Ltd. FAU - Gligorov, Joseph AU - Gligorov J AD - Institut Universitaire de Cancerologie AP-HP Sorbonne Universite, Alliance Pour la Recherche en Cancerologie, Inserm U938, Paris, France. Electronic address: joseph.gligorov@aphp.fr. FAU - Pivot, Xavier AU - Pivot X AD - ICANS, Strasbourg, France. FAU - Ataseven, Beyhan AU - Ataseven B AD - Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany; Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, Germany. FAU - De Laurentiis, Michelino AU - De Laurentiis M AD - Division of Breast Oncology, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Naples, Italy. FAU - Jung, Kyung Hae AU - Jung KH AD - Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. FAU - Manikhas, Alexey AU - Manikhas A AD - Oncology Hospital of St. Petersburg, St. Petersburg, Russia. FAU - Abdel Azim, Hamdy AU - Abdel Azim H AD - Clinical Oncology Department, Cairo University, Cairo, Egypt. FAU - Gupta, Kushagra AU - Gupta K AD - IQVIA RDS India Pvt Ltd, Bangalore, India. FAU - Alexandrou, Ari AU - Alexandrou A AD - F. Hoffmann-La Roche Ltd., Welwyn, United Kingdom. FAU - Herraez-Baranda, Luis AU - Herraez-Baranda L AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Tosti, Nadia AU - Tosti N AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Restuccia, Eleonora AU - Restuccia E AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. LA - eng PT - Journal Article DEP - 20220317 PL - Netherlands TA - Breast JT - Breast (Edinburgh, Scotland) JID - 9213011 RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - P188ANX8CK (Trastuzumab) SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - *Breast Neoplasms/metabolism MH - Chemotherapy, Adjuvant MH - Clinical Trials, Phase III as Topic MH - Disease-Free Survival MH - Female MH - Humans MH - Injections, Subcutaneous MH - Receptor, ErbB-2/metabolism MH - Trastuzumab/therapeutic use PMC - PMC9249556 OTO - NOTNLM OT - Breast neoplasms OT - Disease-free survival OT - Follow-up studies OT - Receptor ErbB2 OT - Safety OT - Trastuzumab COIS- The study was funded by F. Hoffmann-La Roche Ltd. AA, LHB, NT, and ER are employees of and hold stock in F. Hoffmann-La Roche Ltd. JG reports grants, personal fees and non-financial support from Roche-Genentech, personal fees and non-financial support from Novartis, personal fees from Onxeo, personal fees from Daiichi Sankyo, personal fees from MSD, grants, personal fees and non-financial support from Eisai, grants, personal fees and non-financial support from Genomic Health, personal fees from Ipsen, personal fees from Macrogenics, grants, personal fees and non-financial support from Pfizer, outside the submitted work. KG is an employee of IQVIA RDS India Pvt. Ltd., Bangalore, India and external business partner consultant for F. Hoffmann-La Roche Ltd. BA reports personal fees and nonfinancial support from Roche, personal fees from Amgen, personal fees from AstraZeneca, personal fees and non-financial support from Tesaro/GSK, personal fees from Clovis, personal fees from Celgene, nonfinancial support from PharmaMar, personal fees and nonfinancial support from MSD, and personal fees from Novartis, outside the submitted work. KHJ reports personal fees from AstraZeneca, Celgene, Novartis, Roche, Pfizer, and Takeda. MDL reports personal fees from Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Eli Lilly, Amgen, and Pierre Fabre, MSD, Genomic Health, Daiichi-Sankyo, Gilead, and Seagen, outside the submitted work. XP and AM report no disclosures. HAA reports research funds from Pfizer, MSD, and ASZ; serves on the speaker bureau of Roche, MSD, BMS, Bayer, Lilly, Novartis, Pfizer, ASZ, and Amgen. EDAT- 2022/04/30 06:00 MHDA- 2022/06/29 06:00 PMCR- 2022/03/17 CRDT- 2022/04/29 22:16 PHST- 2021/09/07 00:00 [received] PHST- 2022/01/27 00:00 [revised] PHST- 2022/03/03 00:00 [accepted] PHST- 2022/04/30 06:00 [pubmed] PHST- 2022/06/29 06:00 [medline] PHST- 2022/04/29 22:16 [entrez] PHST- 2022/03/17 00:00 [pmc-release] AID - S0960-9776(22)00042-X [pii] AID - 10.1016/j.breast.2022.03.001 [doi] PST - ppublish SO - Breast. 2022 Aug;64:151-158. doi: 10.1016/j.breast.2022.03.001. Epub 2022 Mar 17.