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Background: The wide use of antibody‐drug conjugates (ADCs) is transforming the cancer‐treatment landscape. Understanding the treatment‐related adverse events (AEs) of ADCs is crucial for their clinical application. We conducted a meta‐analysis to analyze the profile and incidence of AEs related to ADC use in the treatment of solid tumors and hematological malignancies. Methods: We searched the PubMed, Embase, and Cochrane Library databases for articles published from January 2001 to October 2022. The overall profile and incidence of all‐grade and grade ≥ 3 treatment‐related AEs were the primary outcomes of the analysis. Results: A total of 138 trials involving 15,473 patients were included in this study. The overall incidence of any‐grade treatment‐related AEs was 100.0% (95% confidence interval [CI]: 99.9%–100.0%; I2 = 89%) and the incidence of grade ≥ 3 treatment‐related AEs was 6.2% (95% CI: 3.0%–12.4%; I² = 99%). Conclusions: This study provides a comprehensive overview of AEs related to ADCs used for cancer treatment. ADC use resulted in a high incidence of any‐grade AEs but a low incidence of grade ≥ 3 AEs. The AE profiles and incidence differed according to cancer type, ADC type, and ADC components. [ABSTRACT FROM AUTHOR]

Numerous studies have reported the efficacy of antibody–drug conjugates (ADCs) for treating breast cancer. However, during cytotoxic drug treatment, long-term disabling fatigue is common. Moreover, studies in the relevant literature have indicated that fatigue can significantly increase the incidence of depression and sleep disorders. Therefore, this meta-analysis aims to evaluate the incidence of fatigue in breast cancer survivors treated with ADCs. PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched for articles and conference abstracts published before March 16, 2023. Further, two authors independently extracted data from the included studies. The primary outcome of this study was the incidence of all-grade fatigue caused by the use of ADCs in patients with breast cancer. Finally, a random-effects model was used to calculate the incidence and 95% confidence intervals (CIs) of the outcome. Overall, 7963 patients from 31 studies were included in this meta-analysis to assess the incidence of fatigue caused by the use of approved and marketed ADCs in patients with breast cancer. Notably, the incidence of all-grade fatigue during ADC monotherapy was 39.84% (95% CI, 35.09%–44.69%). In subgroup analyses, among ADCs, the incidence of trastuzumab deruxtecan-induced fatigue was the highest, with an all-grade fatigue incidence of 47.05% (95% CI, 42.38%–51.75%). Meanwhile, the incidence of trastuzumab emtansine (T-DM1)-induced all-grade fatigue was 35.17% (95% CI, 28.87%–41.74%), which was the lowest among ADCs. Further, the incidence of all-grade fatigue due to sacituzumab govitecan was 42.82% (95% CI, 34.54%–51.32%), which was higher than that due to T-DM1. Moreover, the incidence of fatigue was higher with T-DM1 combination therapy than with monotherapy. Clinicians have highlighted the high incidence of ADC-related fatigue and its negative impact on patients' physical and mental health, making fatigue an important research variable. The results of this study will further contribute to a comprehensive understanding of ADCs, which have some clinical importance and are of great benefit to patients with breast cancer. [Display omitted] • This is the first meta-analysis assessing the fatigue occurrence rates in breast cancer survivors undergoing ADC drug treatment. • Breast cancer patients undergoing ADC drug treatment experience a higher incidence of all-grade fatigue events. Among them, T-DXd exhibits the highest fatigue occurrence rate,T-DM1 having the lowest fatigue occurrence rate. • The fatigue incidence rate is higher in the combination therapy group compared to the monotherapy group. • The fatigue occurrence rate in phase I and II clinical trials is higher than that in phase III clinical trials. [ABSTRACT FROM AUTHOR]

Antibody–drug conjugates (ADCs) have demonstrated significant efficacy in treating solid tumors. However, the occurrence of ADC drug-associated pneumonitis can limit the use of ADCs or have severe consequences, and we know comparatively little about this. PubMed, EMBASE, and the Cochrane library were exhaustively searched for articles and conference abstracts published before September 30, 2022. Two authors independently extracted data from the included studies. A random-effects model was used to conduct a meta-analysis of the relevant outcomes. Forest plots reflected the incidence rates from each study, and binomial methods were used to calculate the 95 % confidence interval. This meta-analysis included 7732 patients from 39 studies and evaluated the incidence of ADCs drug-associated pneumonitis which have received market approval for the treatment of solid tumors. The total incidence of solid tumors for all-grade pneumonitis was 5.86 % (95 % CI, 3.54–8.66 %) and for grade ≥3 was 0.68 % (95 % CI, 0.18–1.38 %). The incidence of all-grade pneumonitis was 5.08 % (95 % CI, 2.76–7.96 %) and for grade ≥3 was 0.57 % (95 % CI, 0.10–1.29 %) with ADC monotherapy. The incidence of all-grade and grade ≥3 pneumonitis in trastuzumab deruxtecan (T-DXd) was 13.58 % (95 % CI, 9.43–18.29 %) and 2.19 % (95 % CI, 0.94–3.81 %), respectively, the highest in ADC therapy. Total incidence of all-grade pneumonitis was 10.58 % (95 % CI, 4.34–18.81 %) and for grade ≥3 pneumonitis was 1.29 % (95 % CI, 0.22–2.92 %) with ADC combination therapy. The incidence of pneumonitis was higher with combination therapy than with monotherapy in both all-grade and grade ≥3 groups, but there was no statistical significance (P =.138 and P =.281, respectively). The incidence of ADC-associated pneumonitis in non-small cell lung cancer (NSCLC) was 22.18 % (95 % CI, 2.14–52.61 %), the highest among solid tumors. The 11 included studies reported 21 pneumonitis-related deaths. Our findings will assist clinicians in choosing the optimal therapeutic options for patients with solid tumors treated with ADCs. [Display omitted] • This is the first meta-analysis to assess the incidence of pneumonitis caused by approved antibody–drug conjugates (ADCs). • Patients with solid tumors had a higher incidence of all-grade ADC drug-associated pneumonitis, grade ≥3 was relatively rare. • The incidence of pneumonitis varies according to drug and tumor type. [ABSTRACT FROM AUTHOR]