Incidence and risk of treatment-related fatal adverse events in cancer patients treated with antibody conjugated drugs: a systematic review and meta-analysis of randomized controlled trails

Antibody-drug conjugates (ADCs) have radically transformed the therapeutic landscape for cancer treatment, but little is known about the treatment-related fatal adverse events (FAEs). We aimed to comprehensively investigate the safety of ADCs regarding treatment-related FAEs. We conducted a systematic search of PubMed, Embase, and the Cochrane database for randomized controlled trials (RCTs) of ADCs. The meta-analysis assessed the incidence of treatment-related FAEs and the odds ratio (OR) in the ADCs group compared with the control group. A total of 49 RCTs involving 13,052 patients treated with ADCs were included. The incidence of treatment-related FAEs in the ADCs group was 0.62% (95% CI = 0.36-1.08), while the control group was 0.52% (95% CI = 0.29-0.95)，with an OR of 1.41 (95% CI = 1.12-1.79; <i>p</i> &lt; 0.05). In the subgroup analysis by drug and cancer type, gemtuzumab ozogamicin, which for acute myeloid leukemia were associated with a higher risk of treatment-related FAEs compared to controls (OR = 1.63; 95% CI = 1.12-2.36; <i>p</i> &lt; 0.05). There was no evidence of publication bias observed. The meta-analysis of RCTs found that ADCs were associated with an increased risk of treatment-related FAEs compared with the control group. Moreover, the occurrence of treatment-related FAEs was associated with specific types of ADCs.