Researchers have characterized treatment-related adverse events (TRAEs) reported in clinical trials of antibody-drug conjugates (ADCs).
The team found that patients with breast cancer had the highest rate of all-grade TRAEs, and those with lymphoma had the highest rate of grade 3 or higher TRAEs.
The ADC with the highest rate of all‐grade TRAEs was trastuzumab deruxtecan, and the ADC with the highest rate of grade 3 or higher TRAEs was brentuximab vedotin.
These results, from a systematic review and meta-analysis, were published in Cancer.
The analysis included reports from 169 clinical trials encompassing 22,492 patients. Multiple types of ADCs were included, and several cancer types were represented.
Overall, there were more than 600 types of adverse events reported across the trials. The overall incidence of TRAEs was 91.2%, and the incidence of grade 3 or higher TRAEs was 46.1%. The incidence of treatment discontinuation due to TRAEs was 13.2%, and the rate of fatal TRAEs was 1.3%.
The most common all-grade TRAEs were lymphopenia (53.0%), nausea (44.1%), neutropenia (43.7%), blurred vision (40.5%), and peripheral neuropathy (39.6%).
The most common grade 3 or higher TRAEs were neutropenia (31.2%), hypoesthesia (23.3%), thrombocytopenia (22.6%), febrile neutropenia (21.2%), and lymphopenia (21.0%).
The ADCs with the highest rates of all‐grade TRAEs were trastuzumab deruxtecan (98.0%), polatuzumab vedotin (97.7%), sacituzumab govitecan (97.1%), patritumab deruxtecan (96.3%), tisotumab vedotin (96.0%), and trastuzumab emtansine (95.7%).
The ADCs with the highest rates of grade 3 or higher TRAEs were brentuximab vedotin (72.9%), inotuzumab ozogamicin (68.0%), sacituzumab govitecan (61.1%), polatuzumab vedotin (60.7%), belantamab mafodotin (56.8%), and glembatumumab vedotin (56.6%).
The highest mean incidences of all-grade TRAEs were seen in patients with breast cancer (97.2%), urinary cancer (93.9%), and lymphoma (91.0%). The highest mean incidences of grade 3 or higher TRAEs were seen in patients with lymphoma (65.4%), leukemia (62.4%), and lung cancer (51.8%).
Subgroup analyses suggested that several patient groups had a higher risk of all‐grade TRAEs, including those with breast cancer, those treated with topoisomerase I inhibitor-based ADCs (vs pyrrolobenzodiazepine‐based ADCs), and those who received anti‐HER2 ADCs (vs anti‐CD19 ADCs).
However, there was no significant difference in the risk of grade 3 or higher TRAEs across subgroups.
“In the absence of consistency in safety data reporting on oncology drugs, this meta‐analysis summarizes the incidence of all common treatment‐related adverse events for ADC therapy and details the treatment‐related causes of treatment cessation and death,” the researchers wrote. “This global overview of ADC adverse events serves as a reference for clinicians and may guide clinical practice.”
Zhu Y, Liu K, Wang K, Zhu H. Treatment‐related adverse events of antibody–drug conjugates in clinical trials: A systematic review and meta‐analysis. Cancer. Published online November 21, 2022. doi:10.1002/cncr.34507