Toxicity profiles of antibody drug conjugates for anticancer treatment: a systematic review and meta-analysis
A partir d'une revue systématique de la littérature (20 études, 10 075 patients), cette méta-analyse évalue les symptômes des patients atteints d'un cancer traité par conjugués anticorps-médicaments
Antibody-drug conjugates (ADCs) are attractive targeted agents in anticancer treatment with their unique mechanism of action and reduced toxicity. Little is known about the spectrum of adverse events associated with ADCs, despite tens of clinical trials.A systematic review of randomized controlled trials evaluating ADCs efficacy in anticancer treatment was conducted. PubMed, EMBASE, and ClinicalTrial.gov were searched for relevant studies. Meta-analyses assessed the odds ratios (ORs) of 12 treatment-related symptoms and toxicities in ADC-treated patients compared to those receiving other anticancer agents without ADCs. All-grade and high-grade (grade 3 or higher) toxicities were examined.20 studies involving 10,075 patients were included. Compared with control groups, ADCs were associated with a higher risk for all-grade fatigue (OR, 1.25; 95% CI, 1.08-1.45), anorexia (OR, 1.36 [1.09-1.69]), nausea (OR, 1.46 [1.09-1.97]) and sensory neuropathy (OR, 2.18 [1.27-3.76]) as treatment-related symptoms. Patients treated with ADCs had a significantly lower risk of all-grade febrile neutropenia (OR, 0.46 [0.22-0.96]). Conversely, they had a higher risk of thrombocytopenia (OR, 2.07 [1.00-4.31]), increased alanine aminotransferase (OR, 2.51 [1.84-3.40]), and increased aspartate aminotransferase (OR, 2.83 [2.04-3.93]). Subgroup analysis showed a similar toxicity profile when comparing the solid tumors vs hematologic malignancy groups and the ADC vs ADC plus chemotherapy groups, except for some neurologic and hematologic adverse events.This comprehensive profile of adverse events associated with ADC-based treatment shows an increase in various types of all-grade treatment-related symptoms and adverse events although no increase in high-grade adverse events was seen.