Efficacy and safety of antibody-drug conjugates in triple-negative and HER-2 positive breast cancer: A systematic review and meta-analysis of clinical trials.

Abstract

Breast cancer (BC) is the 2nd most common cause of cancer-related deaths. Antibody-drug conjugates (ADCs) are monoclonal antibodies linked to cytotoxic agents and are directed towards a specific tumor protein. Therefore, they are more potent and can have relatively less toxicity. In this meta-analysis, we assessed the efficacy and safety of ADCs in breast cancer. We searched PubMed, Cochrane, Web of Science, and clinicaltrials.gov for relevant studies and included 7 randomized clinical trials (N = 5,302) and 7 non-randomized clinical trials (N = 658). R programming language software was used to conduct this meta-analysis. In 4 RCTs on HER-2 positive BC (N = 2,825), the pooled HR of PFS and OS was 0.72 (95% CI = 0.61-0.84, I2 = 71%) and 0.73 (95% CI = 0.64-0.84, I2 = 20%), respectively in favor of ADCs versus chemotherapy. In RCT on triple negative BC (N = 468), HR of PFS and OS were 0.55 (95%CI = 0.51-0.61) and 0.59 (95% CI = 0.54-0.66), respectively, in favor of saci-gov versus chemotherapy. In RCT on HER-2 positive residual invasive BC, HR of recurrence/death was 0.61 (95% CI = 0.54-0.69) in favor of ADC versus chemotherapy. In an RCT (N = 524), the HR of PFS and OS were 0.28 (95% CI = 0.22-0.37) and 0.55 (95%CI = 0.36-0.86), respectively, in favor of trastuzumab-deruxtecan (T-der) as compared to trastuzumab-emtansine (T-DM1). Anemia, rash, diarrhea, fatigue, hypertension, thrombocytopenia, and elevated aminotransferases were the common ≥grade 3 adverse events reported in 4%, 1%, 2%, 1%, 2%, 9%, and 3% of the patients, respectively. ADCs were more effective than single and double agent chemotherapy in patients with HER-2 positive or triple negative BC. Among ADCs, T-der was more effective than T-DM1.