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Meta-Analysis
. 2025 Jun;55(6):e70001.
doi: 10.1111/eci.70001. Epub 2025 Feb 13.

Adverse events and impact on quality of life of antibody-drug conjugates in the treatment of metastatic breast cancer: A systematic review and meta-analysis

Marta Perachino  1   2   3 , Eva Blondeaux  4 , Chiara Molinelli  1   2 , Tommaso Ruelle  1   2 , Irene Giannubilo  1   2 , Luca Arecco  1   2 , Simone Nardin  1   2 , Maria Grazia Razeti  1   2 , Roberto Borea  1   2 , Diletta Favero  1   2 , Chiara Lanzavecchia  1   2 , Edoardo Chiappe  1   2 , Loredana Tomasello  1   5 , Elene Mariamidze  1   6 , Kristina Jankovic  7 , Mihaela Stana  8 , Silvia Ottonello  9 , Graziana Scavone  1 , Luciana de Moura Leite  10 , Stefano Spinaci  11 , Cristina Saura  3 , Matteo Lambertini  1   2
Affiliations
Meta-Analysis

Adverse events and impact on quality of life of antibody-drug conjugates in the treatment of metastatic breast cancer: A systematic review and meta-analysis

Marta Perachino et al. Eur J Clin Invest. 2025 Jun.

Abstract

Background: Antibody-drug conjugates are novel effective therapies for metastatic breast cancer. Nevertheless, their toxicity profile can significantly affect patients' quality of life over time.

Methods: This is a systematic review and meta-analysis of randomized controlled trials of antibody-drug conjugates currently approved for the treatment of metastatic breast cancer [trastuzumab-emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab-govitecan (SG)] versus standard therapy to evaluate the risk of adverse events, discontinuation rate due to toxicity, impact on quality of life according to EORTC QLQ-C30 scale and subdomains. Relative risks (RR) and hazard ratios (HR) with 95% CIs were calculated using random effects models.

Results: Nine trials with a total of 5753 patients were included. The most common adverse events of any grade for T-DM1 included thrombocytopenia (RR 7.14, 95% CI 4.13-12.36) and increased alanine-transaminase (ALT) (RR 2.04, 95% CI 1.43-2.91), for T-DXd were nausea (RR 2.39, 95% CI 1.90-3.00) and anemia (RR 1.55, 95% CI 1.27-1.90), while for SG were neutropenia (RR 1.30, 95% CI 1.14-1.49), diarrhea (RR 3.62, 95% CI 2.97-4.42) and nausea (RR1.90, 95% CI 1.65-2.19). Severe adverse events such as interstitial lung disease and left ventricular dysfunction were peculiar of T-DXd. Antibody-drug conjugates significantly delayed clinical deterioration of global health status by EORTC QLQ-C30 (HR .71, 95% CI .59-.86), physical, emotional and social functioning, pain and fatigue symptoms.

Conclusions: This meta-analysis offers consolidated data on adverse events associated with antibody-drug conjugates and their effects on patients' quality of life, emphasizing differences based on the specific agent. These findings underscore the critical need for effective strategies to prevent, diagnose and manage these toxicities.

Keywords: adverse events; antibody‐drug conjugate; breast cancer; quality of life; toxicity.

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Conflict of interest statement

MP reported honoraria from Daiichi Sankyo. EB reported receiving research funding (to her institution) from Gilead, speaker fees from Eli Lilly. CS reports consulting fees, honoraria or meeting/travel support from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Genentech,Gilead, Lilly, MediTech, Menarini, MSD Spain, Novartis, Pfizer, Philips Healthcare, Pharmalex, Pierre Fabre, Puma Biotechnology, Roche, Seagen, Synthon and Zymeworks.ML: advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, Menarini; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Menarini, AstraZeneca; travel Grants from Gilead, Daiichi Sankyo, Roche; research funding (to the Institution) from Gilead all outside the submitted work.

Figures

FIGURE 1
FIGURE 1
Prisma flow diagram depicting the search strategy in the systemic review literature search.
FIGURE 2
FIGURE 2
Relative risks of developing AEs of interest per each ADC. (A) Trastuzumab‐emtansine. (B) Trastuzumab‐deruxtecan. (C) Sacituzumab‐govitecan.
FIGURE 3
FIGURE 3
Hazard ratios for each HR‐QoL outcome considered in the analysis per each ADC.
See this image and copyright information in PMC

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