title: Does dual HER-2 blockade treatment increase the risk of severe toxicities of special interests in breast cancer patients: A meta-analysis of randomized controlled trials.
abstract: Although dual HER-2 blockade treatment could offer greater clinical efficacy in breast cancer, the risk of severe toxicities of special interest related to this combined regimen in breast cancer remained unknown. We systematically searched public databases (MEDLINE, EMBASE, Cochrane library) to identify relevant studies that comparing anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) with dual HER-2 blockade treatment (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) in breast cancer. A total of 11,941 breast cancer patients from 9 trials were included for analysis. Meta-analysis showed that dual HER2 blockade treatment significantly increased the risk of severe diarrhea (OR 2.52, p<0.001) and treatment discontinuation (OR 1.52, p=0.014), but not for severe rash (OR 1.06, p=0.81), liver toxicities (OR 1.16, p=0.28), CHF (OR 1.46, p=0.09), LVEF decline (OR 1.09, p=0.40) and FAEs (OR 0.97, p=0.91). Similar results were observed in sub-group analysis according to anti-HER2 regimens in terms of severe diarrhea and treatment discontinuation. Additionally, trastuzumab plus lapatinib significantly increased the risk of LVEF decline in comparison with lapatinib alone (OR 1.48, p=0.002). Our analysis indicated that dual anti-HER2 blockade treatment significantly increased the risk of developing severe diarrhea and treatment discontinuation in comparison with anti-HER2 monotherapy. These were no evidence of an increased risk of fatal adverse events with dual-HER2 blockade treatment.
authors.affiliation: Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Hao
authors.affiliation: Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Wuguo
authors.initials: W
authors.lastname: Tian
authors.affiliation: Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Lingji
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Jianjie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Donglin
authors.initials: D
authors.lastname: Luo
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003967:Diarrhea / Q000139:chemically induced; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D000077341:Lapatinib; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012307:Risk Factors; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C485206:pertuzumab
keywords: Her2; adverse events; breast cancer; dual Her-2 blockade; meta-analysis