Efficacy and Safety of Anti-HER2 Agents in Combination With Chemotherapy for Metastatic HER2-Positive Breast Cancer Patient: A Network Meta-Analysis

Abstract

BackgroundThe presence of anti-HER2 agents, such as trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1), significantly improved the prognosis of metastatic HER2-positive (HER2+) breast cancers (BC). However, drug resistance and disease progression are still common. In order to further improve the treatment efficacy, new clinical trials about anti-HER2 agents in combination with chemotherapy are growing rapidly. We conducted the network meta-analysis to synthesize evidences of clinical trials to identify the best therapy for metastatic HER2+ BC.MethodsA systematic search of randomized controlled trials regarding anti-HER2 agents in combination with chemotherapy for advanced or metastatic breast cancers up to May 2020 was conducted in Embase, PubMed, and the Cochrane Library. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), objective response rate (ORR), and safety. Bayesian network meta-analysis was conducted to synthesize the results and rank the therapies.ResultsTwenty-six studies, including 16 studies for first-line treatments and 10 studies for second- or later-line treatments were included in the network meta-analysis. For first-line studies, the THP (taxanes + trastuzumab + pertuzumab) regimen exhibited the highest probability to be the optimal treatment in all efficacy outcomes and moderate safety. For second- or later-line studies, the T-DM1 and XHTuC (capecitabine + trastuzumab + tucatinib) regimens ranked top two in all efficacy outcomes according to the surface under the cumulative ranking (SUCRA) results. T-DM1 ranked first in PFS and OS whereas XHTuC ranked first in ORR. The safety outcomes of T-DM1 and XHTuC were acceptable.ConclusionsTHP was still the optimal first-line treatment for metastatic HER2+ BC. T-DM1 and XHTuC were recommended for second-line treatments.Systematic Review RegistrationINPLASY.com, identifier (INPLASY202090086).

Demographic and Clinical Features of Patients with Metastatic Breast Cancer: A Retrospective Multicenter Registry Study of the Turkish Oncology Group

“…Despite bearing an unfavorable patient profile enriched in a younger population with CNS involvement, the improvement in outcome in the HER2+ dnMBC most likely reflects the higher rates of access to combined trastuzumab and pertuzumab after 2015. Our results are in parallel with several registry data showing a significant outcome difference in patients with de novo as compared to recurrent HER2+ MBC which have reported superior survival rates only in the HER2+ subgroup [ 18 , 34 , 35 , 36 , 37 ]. A striking finding in our cohort was the favorable prognosis in the luminal B-HER2+ subgroup as compared to all pathologic subtypes, which has been consistently observed by others, reflecting the use of sequential endocrine therapy following chemotherapy and HER2 blockade in routine clinical practice [ 9 , 38 , 39 ].…”

Therapeutic efficacy of antibody-drug conjugates targeting GD2-positive tumors

“…Trastuzumab emtansine (T-DM1) shows significant efficacy and safety benefit as second-line treatment of HER2-positive breast cancer compared with a combination of trastuzumab and chemotherapy. 5 Newer generation trastuzumab deruxtecan demonstrates improved potency versus T-DM1 due to a cleavable linker and a higher number of exatecan derivative molecules that exert bystander cell killing in heterogeneous tumors with varying levels of HER2 expression. 6 Approval of sacituzumab govitecan that targets a different marker Trop-2 in triple-negative breast cancer (TNBC) 3 further emphasizes the importance of ADCs in breast cancer therapy.…”

The protein corona reduces the anticancer effect of graphene oxide in HER-2-positive cancer cells

“…As a model of HER-2 positive cancer cells, we used SK-BR-3 cancer cells that over-express HER-2 and tend to grow and spread faster than other breast cancer subtypes. Several pharmacological treatments have been developed to target specifically HER-2 protein and inhibit its function, such as Trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1) [32]. Although HER-2 targeted drugs have significantly improved survival outcomes for HER-2-positive breast cancer patients, some of them may show no response or develop drug resistance after a period of treatment.…”

“…Several pharmacological treatments have been developed to target specifically HER-2 protein and inhibit its function, such as trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1). 32 Although HER-2 targeted drugs have significantly improved survival outcomes for HER-2-positive breast cancer patients, some of them may show no response or develop drug resistance after a period of treatment. Thus, there is still a need to develop new anti HER-2 anticancer agents and understand their modes of action.…”