Is ADC a rising star in solid tumor? An umbrella review of systematic reviews and meta-analyses
Abstract Background 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...
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BMC
2025-02-01
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| Online Access: | https://doi.org/10.1186/s12885-025-13726-8 |
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| author | Hua Wei Yongjun Zhang Yun Lu Ya Zou Lu Zhou Xiaoli Qin Qian Jiang |
| author_facet | Hua Wei Yongjun Zhang Yun Lu Ya Zou Lu Zhou Xiaoli Qin Qian Jiang |
| author_sort | Hua Wei |
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| description | Abstract Background 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. Objective To comprehensively assess and overview the efficacy and safety of antibody-drug conjugates for the treatment of solid tumors. Design An umbrella review of systematic reviews and meta-analyses. Methods 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. Results 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. Conclusions 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. Systematic review registration PROSPERO CRD 42,024,564,517. |
| format | Article |
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| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-fb7430c021a24da381e244da02ca23212025-08-20T02:01:35ZengBMCBMC Cancer1471-24072025-02-0125111210.1186/s12885-025-13726-8Is ADC a rising star in solid tumor? An umbrella review of systematic reviews and meta-analysesHua Wei0Yongjun Zhang1Yun Lu2Ya Zou3Lu Zhou4Xiaoli Qin5Qian Jiang6Department of Pharmacy, Chengdu Second People’s HospitalDepartment of Anesthesiology, Chengdu Seventh People’s Hospital (Affiliated Cancer Hospital of Chengdu Medical College)Department of Pharmacy, Chengdu Second People’s HospitalDepartment of Pharmacy, Chengdu Second People’s HospitalDepartment of Pharmacy, Chengdu Second People’s HospitalDepartment of Pharmacy, The Third People’s Hospital of ChengduDepartment of Pharmacy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, University of Electronic Science and Technology of ChinaAbstract Background 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. Objective To comprehensively assess and overview the efficacy and safety of antibody-drug conjugates for the treatment of solid tumors. Design An umbrella review of systematic reviews and meta-analyses. Methods 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. Results 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. Conclusions 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. Systematic review registration PROSPERO CRD 42,024,564,517.https://doi.org/10.1186/s12885-025-13726-8Antibody-drug conjugatesADCsSolid tumorEfficacySafetyUmbrella Review |
| spellingShingle | Hua Wei Yongjun Zhang Yun Lu Ya Zou Lu Zhou Xiaoli Qin Qian Jiang Is ADC a rising star in solid tumor? An umbrella review of systematic reviews and meta-analyses BMC Cancer Antibody-drug conjugates ADCs Solid tumor Efficacy Safety Umbrella Review |
| title | Is ADC a rising star in solid tumor? An umbrella review of systematic reviews and meta-analyses |
| title_full | Is ADC a rising star in solid tumor? An umbrella review of systematic reviews and meta-analyses |
| title_fullStr | Is ADC a rising star in solid tumor? An umbrella review of systematic reviews and meta-analyses |
| title_full_unstemmed | Is ADC a rising star in solid tumor? An umbrella review of systematic reviews and meta-analyses |
| title_short | Is ADC a rising star in solid tumor? An umbrella review of systematic reviews and meta-analyses |
| title_sort | is adc a rising star in solid tumor an umbrella review of systematic reviews and meta analyses |
| topic | Antibody-drug conjugates ADCs Solid tumor Efficacy Safety Umbrella Review |
| url | https://doi.org/10.1186/s12885-025-13726-8 |
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