Differences observed in adverse events of antibody-drug conjugates
Click Here to Manage Email Alerts
Use of different antibody-drug conjugates resulted in a variety of significant and in some cases serious treatment‐associated adverse events, according to results of a systematic review and meta-analysis published in Cancer.
The findings provide a reference for clinicians and patients on how to address toxicities of antibody-drug conjugates in clinical practice, researchers concluded.
Background and methods
"Antibody-drug conjugates have complex molecular structures and have been tested in numerous clinical trials,” Hong Zhu, PhD, researcher in the department of oncology at Central South University in China, and colleagues wrote. However, a better understanding is needed of their toxicity mechanisms when used in medical practice, according to study background.
Researchers queried PubMed, Embase, Cochrane and Web of Science for studies of antibody-drug conjugates published between Jan. 1, 2000, and June 7, 2022 and identified 2,511 records from 169 clinical trials that included 22,492 patients.
They used a random-effects model with logit transformation to analyze final incidence of adverse events and I² statistics to evaluate heterogeneity between studies.
Incidence and 95% CIs for all-grade and grade 3 or higher treatment-associated adverse events and differences between treatments, molecular structures and cancer types served as the primary outcome.
Findings
Results showed overall incidence of 91.2% (95% CI, 90.7-91.7; I² = 95.9%) for all-grade treatment-associated adverse events and 46.1% (95% CI, 45.2-47; I² = 96.3%) for grade 3 or higher events. Researchers reported an overall incidence of treatment-associated death of 1.3% (95% CI, 1.1-1.5; I² = 68.2%).
All‐grade adverse events with the highest incidence included lymphopenia (53%; 95% CI, 48.7-57.3), followed by nausea (44.1%; 95% CI, 43.2-44.9), neutropenia (43.7%; 95% CI, 42.6-44.9), blurred vision (40.5%; 95% CI, 37.4-43.6) and peripheral neuropathy (39.6%; 95% CI, 38.2-41.1).
Moreover, common grade 3 or higher adverse events included neutropenia (31.2%; 95% CI, 30.2-32.3), hypoesthesia (23.3%; 95% CI, 10.6-35.9), thrombocytopenia (22.6%; 95% CI, 21.3-23.9), febrile neutropenia (21.2%; 95% CI, 19.3-23.1) and lymphopenia (21%; 95% CI, 18.2-23.7).
Certain antibody-drug conjugates appeared associated with higher average incidences of adverse events, researchers noted.
Implications
Further investigation into the drivers of antibody-drug conjugate toxicity is warranted, researchers wrote.
“Payload-related toxicity and molecular target‐related toxicity have different toxicity characteristics,” they wrote. “We can also select patient groups for optimal [antibody-drug conjugate] dose and management based on drug and payload types, molecular target expression and distribution, and cancer type by subgroup analysis.”
References :
- Analysis reveals adverse effects of complex cancer therapies called antibody drug conjugates (press release). Published Nov. 21, 2022. Accessed Nov. 21, 2022.
- Zhu Y, et al. Cancer. 2022;doi:10.1002/cncr.34507.
Collapse
Read more about
Click Here to Manage Email Alerts