Is ADC a rising star in solid tumor? An umbrella review of systematic reviews and meta-analyses

Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the potency of highly cytotoxic drugs and are known as panaceas, completely changing the treatment paradigm for solid tumors. Compared with other anti-cancer drugs, do they have better efficacy and lower toxicity risks? It is necessary to summarize and analyze the published clinical research data in this area to provide additional evidence-based evidence for clinical practice.

To comprehensively assess and overview the efficacy and safety of antibody-drug conjugates for the treatment of solid tumors.

An umbrella review of systematic reviews and meta-analyses.

Systematic search of eight electronic databases and one registration platform including Embase, PubMed, Cochrane Database of Systematic Reviews (CDSR), Web of Science (WoS), China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wan Fang Data, China Science and Technology Journal Database (VIP) and international prospective register of systematic reviews (PROSPERO) on Aug 1, 2024, to identify relevant systematic reviews or meta-analyses. Three authors completed research screening and data extraction independently. AMSTAR 2 was used to evaluate the methodological quality of the included studies and the Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) was performed to evaluate the quality of the evidence. We examined progression-free survival (PFS), overall survival (OS), objective response rate (ORR) as efficacy endpoints, and the incidence of adverse events (AEs) as safety profiles.

A total of 16 eligible publications, including 32 clinical studies, were included in the umbrella review. The methodological quality of the included study was poor, with 2 articles of moderate-quality (12.5%), 5 articles of low quality (31.25%), and 9 articles of critically low quality (56.25%). Only one third of the evidence was of high quality. Within the included studies, breast cancer accounted for four-fifths, 2 studies were gastric cancer, and 1 study was a solid tumor. The overall results showed that ADCs significantly increased PFS and OS in patients with solid tumors, and the risk of toxicity was within an acceptable range. ado-Trastuzumab emtansine (T-DM1) and Trastuzumab deruxtecan (T-Dxd) treatment of human epidermal growth factor receptor 2(HER2) low/positive advanced metastatic breast cancer significantly prolonged PFS and OS, but the ORR showed a significant advantage. Compared with the chemotherapy group, T-Dxd significantly prolonged OS and PFS in gastric cancer patients, while T-DM1 did not. In other cancer types (ovarian cancer, renal cell carcinoma, and malignant pleural mesothelioma), ADCs tended to extend overall survival or progression-free survival compared with controls, but the difference was not statistically significant.

Based on the available evidence, in breast cancer, ADCs were proved to with significant improvements in prolonging survival time and demonstrates a tolerable safety profile. Meanwhile, ADCs were proved to have enormous potential for the treatment of solid tumors. However, well-designed, multi-center RCTs need to further identify its potential in various solid tumors.

PROSPERO CRD 42,024,564,517.