PMID- 37120775 OWN - NLM STAT- MEDLINE DCOM- 20231102 LR - 20231120 IS - 1591-9528 (Electronic) IS - 1591-8890 (Linking) VI - 23 IP - 7 DP - 2023 Nov TI - Efficacy of anti-HER2 drugs in the treatment of patients with HER2-mutated cancers: a systematic review and meta-analysis. PG - 3205-3216 LID - 10.1007/s10238-023-01072-7 [doi] AB - Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2 mutations are rarely expressed in several cancers, when they occur, they can activate the HER2 signaling pathway. In recent years, studies have shown that anti-HER2 drugs have promising efficacy in patients with HER2 mutations. Based on keywords, we searched databases, such as PubMed, Embase, and Cochrane Library, and the main conference abstracts. We extracted data on objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) from studies on the efficacy of anti-HER2 therapies in patients with HER2-mutated cancers, and analyzed grade 3 or higher adverse events (AEs). We included 19 single-arm clinical studies and 3 randomized controlled trials (RCTs), containing a total of 1017 patients with HER2 mutations, involving seven drugs and nine cancers, and 18 studies enrolled a high proportion of heavily pretreated patients who had received multiple lines of therapy. Our results showed pooled ORR and CBR of 25.0% (range, 3.8-72.7%; 95% CI, 18-32%) and 36.0% (range, 8.3-63.0%; 95% CI, 31-42%) for anti-HER2 therapy in HER2-mutated cancers. The pooled median PFS, OS, DOR were 4.89 (95% CI, 4.16-5.62), 12.78 (95% CI, 10.24-15.32), and 8.12 (95% CI, 6.48-9.75) months, respectively. In a subgroup analysis, we analyzed the ORR for different cancers, showing 27.0, 25.0, 23.0, and 16.0% for breast, lung, cervical, and biliary tract cancers, respectively. ORR analyses were performed for different drugs as monotherapy or in combination, showing 60.0% for trastuzumab deruxtecan (T-DXd), 31.0% for pyrotinib, 26.0% for neratinib combined with trastuzumab, 25.0% for neratinib combined with fulvestrant, 19.0% for trastuzumab combined with pertuzumab, and 16.0% for neratinib. In addition, we found that diarrhoea, neutropenia, and thrombocytopenia were the most common grade >/= 3 AEs associated with anti-HER2 therapeutic agents. In this meta-analysis of heavily pretreated patients with HER2 mutations, anti-HER2 therapies, DS-8201 and trastuzumab emtansine, showed promising efficacy and activity. Anti-HER2 therapies showed different efficacies in different or the same cancer settings and all had a tolerable safety profile. CI - (c) 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Zheng, Yonghui AU - Zheng Y AD - Breast Disease Diagnosis and Treatment Center of Affiliated Hospital, Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China. FAU - Shen, Guoshuang AU - Shen G AD - Breast Disease Diagnosis and Treatment Center of Affiliated Hospital, Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China. FAU - Zhang, Chengrong AU - Zhang C AD - Breast Disease Diagnosis and Treatment Center of Affiliated Hospital, Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China. FAU - Huo, Xingfa AU - Huo X AD - Breast Disease Diagnosis and Treatment Center of Affiliated Hospital, Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China. FAU - Xin, Yuanfang AU - Xin Y AD - Breast Disease Diagnosis and Treatment Center of Affiliated Hospital, Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China. FAU - Fang, Qianqian AU - Fang Q AD - Breast Disease Diagnosis and Treatment Center of Affiliated Hospital, Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China. FAU - Guan, Yumei AU - Guan Y AD - Breast Disease Diagnosis and Treatment Center of Affiliated Hospital, Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China. FAU - Zhao, Fuxing AU - Zhao F AD - Breast Disease Diagnosis and Treatment Center of Affiliated Hospital, Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China. FAU - Ren, Dengfeng AU - Ren D AD - Breast Disease Diagnosis and Treatment Center of Affiliated Hospital, Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China. FAU - Liu, Zhen AU - Liu Z AD - Breast Disease Diagnosis and Treatment Center of Affiliated Hospital, Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China. FAU - Wang, Miaozhou AU - Wang M AD - Breast Disease Diagnosis and Treatment Center of Affiliated Hospital, Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China. FAU - Zhao, Jiuda AU - Zhao J AD - Breast Disease Diagnosis and Treatment Center of Affiliated Hospital, Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China. jiudazhao@126.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20230430 PL - Italy TA - Clin Exp Med JT - Clinical and experimental medicine JID - 100973405 RN - P188ANX8CK (Trastuzumab) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - SE2KH7T06F (Ado-Trastuzumab Emtansine) SB - IM MH - Humans MH - Female MH - Trastuzumab MH - Receptor, ErbB-2/genetics MH - Ado-Trastuzumab Emtansine/therapeutic use MH - *Neoplasms/drug therapy/genetics MH - *Breast Neoplasms/drug therapy MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use OTO - NOTNLM OT - Anti-HER2 therapy OT - Cancer OT - ERBB2 mutation OT - HER2 mutation OT - HER2-mutant EDAT- 2023/04/30 12:42 MHDA- 2023/11/02 12:44 CRDT- 2023/04/30 11:04 PHST- 2022/12/08 00:00 [received] PHST- 2023/04/06 00:00 [accepted] PHST- 2023/11/02 12:44 [medline] PHST- 2023/04/30 12:42 [pubmed] PHST- 2023/04/30 11:04 [entrez] AID - 10.1007/s10238-023-01072-7 [pii] AID - 10.1007/s10238-023-01072-7 [doi] PST - ppublish SO - Clin Exp Med. 2023 Nov;23(7):3205-3216. doi: 10.1007/s10238-023-01072-7. Epub 2023 Apr 30.