PMID- 30396014 OWN - NLM STAT- MEDLINE DCOM- 20191003 LR - 20191007 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 105 DP - 2018 Dec TI - Safety profile of subcutaneous trastuzumab for the treatment of patients with HER2-positive early or locally advanced breast cancer: primary analysis of the SCHEARLY study. PG - 61-70 LID - S0959-8049(18)31404-7 [pii] LID - 10.1016/j.ejca.2018.09.034 [doi] AB - BACKGROUND: Subcutaneous trastuzumab (H SC) is a valuable alternative to the intravenous formulation. This study assessed H SC safety and tolerability in human epidermal growth factor receptor 2 (HER2)+ early/locally advanced breast cancer (EBC/LABC). METHODS: SCHEARLY is a prospective, two-cohort, non-randomised, multicentre Italian trial included in the umbrella study UmbHER1, planning a 1-year treatment with H SC 600 mg in HER2+ EBC/LABC. Patients were sequentially assigned to cohort A (N = 121) and B (N = 119) to receive H SC via a handheld syringe and a single-use injection device, respectively. Adjuvant or neoadjuvant treatment included anthracycline-containing regimens followed by H SC plus taxanes and then alone for 18 cycles totally. RESULTS: Two hundred forty patients were enrolled (adjuvant therapy: 81.7%; neoadjuvant therapy: 18.3%), and 201 completed the treatment (early discontinuation was mainly due to intercurrent adverse events [AEs], 7.5%). Overall, the two cohorts displayed similar safety profiles. From H SC start, the rate of treatment-related AEs in the safety population (N = 228) was 3.9% for grade >/=3 AEs; 0.9% for serious AEs (one pleuropericarditis and one anaphylactic shock, both resolved) and 14.5% for cardiac AEs, the most common being the decreased left ventricular ejection fraction (7.9%; mean reduction from the screening to the follow-up visit was 2.9%). No cases of congestive heart failure occurred. The rate of systemic administration-related reactions and local injection site reactions was 68.0% and 21.9%, respectively, mostly of grade 1-2. CONCLUSIONS: H SC 600 mg confirmed to be a safe and tolerable option as adjuvant/neoadjuvant therapy in patients with HER2+ EBC and LABC. CLINICALTRIALS. GOV IDENTIFIER: NCT01940497. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Zambetti, Milvia AU - Zambetti M AD - Medical Oncology Dept, San Raffaele Scientific Institute, Via Olgettina, 60, 20132 Milan, Italy. Electronic address: milvia.zambetti2018@gmail.com. FAU - Montemurro, Filippo AU - Montemurro F AD - Investigational and Clinical Oncology, Candiolo Cancer Institute, FPO-IRCCS, St. Prov. 142, 10060 Candiolo, Italy. Electronic address: filippo.montemurro@ircc.it. FAU - Morandi, Paolo AU - Morandi P AD - Medical Oncology Dept., Azienda ULSS 12 "Veneziana", Ospedale Dell'Angelo, Via Paccagnella 11, 30174 Mestre-Venezia, Italy. Electronic address: Paolo.Morandi@aulss3.veneto.it. FAU - Zamagni, Claudio AU - Zamagni C AD - SSD Medical Oncology Addari, Policlinico Sant'Orsola Malpighi, Via Pietro Albertoni, 15, 40138 Bologna, Italy. Electronic address: claudio.zamagni@aosp.bo.it. FAU - Brandes, Alba A AU - Brandes AA AD - Medical Oncology Dept, AUSL Bologna-ISNB, Via Altura, 3, 40139 Bologna, Italy. Electronic address: a.brandes@ausl.bologna.it. FAU - Bisagni, Giancarlo AU - Bisagni G AD - IRCCS Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia, Viale Risorgimento, 80, 42123 Reggio Emilia, Italy. Electronic address: Giancarlo.Bisagni@asmn.re.it. FAU - Cagossi, Katia AU - Cagossi K AD - Division of Medical Oncology, "B.Ramazzini" Hospital, Via Molinari 2, 41012, Carpi, Italy. Electronic address: k.cagossi@ausl.mo.it. FAU - Bengala, Carmelo AU - Bengala C AD - Division of Medical Oncology, Department of Oncology, Misericordia Hospital, Via Senese, 169, 58100 Grosseto, Italy. Electronic address: c.bengala@usl9.toscana.it. FAU - Gori, Stefania AU - Gori S AD - Oncology Dept. IRCCS Sacro Cuore Don Calabria Hospital, Via Don A. Sempreboni, 5, 37024 Negrar, Verona, Italy. Electronic address: stefania.gori@sacrocuore.it. FAU - Iannacone, Claudio AU - Iannacone C AD - SPARC Consulting Srl, Via Archimede 94, 20129 Milan, Italy. Electronic address: claudio.iannacone@sparcconsulting.com. FAU - Stell, Alessia AU - Stell A AD - Roche S.p.A., Viale G.B. Stucchi,110, 20900 Monza, Italy. Electronic address: alessia.stell@roche.com. FAU - Gianni, Luca AU - Gianni L AD - Medical Oncology Dept, San Raffaele Scientific Institute, Via Olgettina, 60, 20132 Milan, Italy. Electronic address: gianni.luca@hsr.it. LA - eng SI - ClinicalTrials.gov/NCT01940497 PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20181103 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Antineoplastic Agents, Immunological) RN - 15H5577CQD (Docetaxel) RN - 80168379AG (Doxorubicin) RN - 8N3DW7272P (Cyclophosphamide) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - P188ANX8CK (Trastuzumab) RN - P88XT4IS4D (Paclitaxel) RN - U3P01618RT (Fluorouracil) SB - IM MH - Adenocarcinoma/*drug therapy/genetics/pathology MH - Antineoplastic Agents, Immunological/administration & dosage/*adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Breast Neoplasms/*drug therapy/genetics/pathology MH - *Chemotherapy, Adjuvant MH - Cyclophosphamide/administration & dosage MH - Docetaxel/administration & dosage MH - Doxorubicin/administration & dosage MH - Female MH - Fluorouracil/administration & dosage MH - Follow-Up Studies MH - *Genes, erbB-2 MH - Heart Diseases/*chemically induced MH - Humans MH - Injections, Subcutaneous MH - Middle Aged MH - *Molecular Targeted Therapy MH - *Neoadjuvant Therapy MH - Neoplasm Invasiveness MH - Paclitaxel/administration & dosage MH - Prospective Studies MH - Receptor, ErbB-2/analysis/genetics MH - Stroke Volume MH - Trastuzumab/administration & dosage/*adverse effects OTO - NOTNLM OT - Cardiotoxicity OT - Early/locally advanced breast cancer OT - HER2 OT - Safety OT - Subcutaneous trastuzumab EDAT- 2018/11/06 06:00 MHDA- 2019/10/08 06:00 CRDT- 2018/11/06 06:00 PHST- 2018/07/05 00:00 [received] PHST- 2018/09/25 00:00 [revised] PHST- 2018/09/25 00:00 [accepted] PHST- 2018/11/06 06:00 [pubmed] PHST- 2019/10/08 06:00 [medline] PHST- 2018/11/06 06:00 [entrez] AID - S0959-8049(18)31404-7 [pii] AID - 10.1016/j.ejca.2018.09.034 [doi] PST - ppublish SO - Eur J Cancer. 2018 Dec;105:61-70. doi: 10.1016/j.ejca.2018.09.034. Epub 2018 Nov 3.