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

Our plain-English summary of Is ADC a rising star in solid tumor? An umbrella review of systematic reviews and meta-analyses, by H. Wei, Y. Zhang, Y. Lu, et al (BMC Cancer, 2025).

The study

• Authors: H. Wei, Y. Zhang, Y. Lu, Y. Zou, L. Zhou, X. Qin, Q. Jiang
• Journal: BMC Cancer
• Published: 2025;25(1):380
• Type of article: Systematic review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2025. The Author(s).

In plain English

This was an umbrella review (a review of systematic reviews and meta-analyses) of antibody-drug conjugates (ADCs), cancer drugs that attach a cell-killing drug to an antibody. It did not study asbestos exposure. The authors searched databases on Aug 1, 2024, and included 16 systematic reviews/meta-analyses covering 32 clinical trials; 14 of the reviews focused on breast cancer. They rated none of the 16 as high methodological quality and 9 as critically low. In HER2-positive breast cancer, T-DM1 significantly prolonged overall and progression-free survival compared with control groups, and T-Dxd likewise in HER2-low or HER2-positive advanced or metastatic breast cancer. In malignant pleural mesothelioma, one included review found anetumab ravtansine showed no significant advantage over chemotherapy in either measure. Some side effects, including liver enzyme rises, nausea and pneumonitis, increased with ADCs, while febrile neutropenia and hair loss were less common. The authors concluded that ADCs bring more options for breast cancer treatment and that large multi-center studies are needed for other solid tumors. They noted that breast cancer dominated the combined results and that heterogeneity was mostly unresolved.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Umbrella review of systematic reviews and meta-analyses of randomized controlled trials. Methodological quality was rated with AMSTAR 2 and evidence quality with GRADE.
• Who was studied: Of 253 records found, 69 full texts were reviewed. 16 systematic reviews/meta-analyses were included, half in English and half in Chinese. Together they contained 102 articles involving 32 clinical trials of patients with solid tumors. Of the 16 reviews, 14 targeted breast cancer and 2 targeted solid tumors. Databases were searched on Aug 1, 2024.
• Exposure: Treatment with antibody-drug conjugates compared with non-ADC therapy. The 11 ADCs included T-DM1, T-Dxd, sacituzumab govitecan, anetumab ravtansine, AGS-16C3F, lifastuzumab vedotin and glembatumumab vedotin. They covered 5 tumor types, including malignant pleural mesothelioma. No asbestos exposure was studied.
• Main results:
  • AMSTAR 2 methodological quality of the 16 included reviews: none high, 2 (12.5%) moderate, 5 (31.25%) low, and 9 (56.25%) critically low.
  • GRADE quality of the 53 outcome indicators: 14 (26.4%) high, 20 (37.7%) moderate, and 19 (35.8%) low.
  • In HER2-positive breast cancer, overall survival and progression-free survival were significantly prolonged in the T-DM1 group compared with control. There was no significant difference in objective response rate.
  • The authors summarized that T-DM1 and T-Dxd significantly prolonged progression-free and overall survival in HER2-low/positive advanced or metastatic breast cancer.
  • In early-stage HER-2 positive breast cancer, neoadjuvant T-DM1 improved the pathological complete response rate (OR = 1.90, 95% CI 1.02 to 3.51, P = 0.04). There was no significant difference in 3-year disease-free survival (OR = 1.16, 95% CI 0.64 to 2.12, P = 0.62).
  • In gastric cancer, patients with HER2 IHC3+ treated with T-Dxd had an overall survival benefit (HR = 0.53, 95% CI 0.28 to 0.78). Patients with HER2 IHC2+/ISH+ did not (HR = 1.15, 95% CI 0.16 to 2.14).
  • One included review evaluated solid tumors other than breast and gastric cancer. In it, anetumab ravtansine showed no significant advantage over chemotherapy in progression-free or overall survival in malignant pleural mesothelioma, and neither did AGS-16C3F in renal cell carcinoma.
  • In one review, treatment-related adverse events were higher in the T-Dxd group than in controls (RR = 6.93, 95% CI 2.06 to 23.25, P = 0.002). Other reviews found no significant difference.
  • ALT, AST, nausea, constipation, left ventricular dysfunction, decreased appetite, pneumonitis and interstitial lung disease, and hypertension increased significantly in ADC groups compared with control groups.
  • Febrile neutropenia and alopecia were significantly less frequent in ADC groups than in control groups.
• The authors' conclusion: The authors concluded that ADCs bring more options for breast cancer treatment. They called for prospective, large-scale, multi-center studies to verify efficacy and safety in solid tumors other than breast cancer.
• Limitations the authors state:
  • Restricting inclusion to reviews of randomized controlled trials meant some ADCs (e.g. tisotumab vedotin, mirvetuximab soravtansine, disitamab vedotin) were not covered.
  • The original studies were not analyzed, so the quality of the evidence depends on the included systematic reviews.
  • Heterogeneity was not resolved in most results.
  • Breast cancer made up a large share of the data and strongly influenced the combined results.

Topics

Medical terms in this study, explained in our Lexicon: Systematic Review, Monoclonal Antibody, Progression-Free Survival, Overall Survival, Stomach Cancer, Trastuzumab, HER2, Chemotherapy.

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