Tolerability and toxicity profiles of antibody-drug conjugates for the treatment of malignant neoplasms: A meta-analysis of randomized clinical trials.

person Susu Zhou Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel., New York, NY info_outline Susu Zhou, Toshiki Kuno, Etsuko Miyagi, Jason Dennis Wright, Hisato Takagi, Yukio Suzuki

Authors person Susu Zhou Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel., New York, NY info_outline Susu Zhou, Toshiki Kuno, Etsuko Miyagi, Jason Dennis Wright, Hisato Takagi, Yukio Suzuki Organizations Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel., New York, NY, Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY, Department of Obstetrics and Gynecology, Yokohama City University Graduate School of Medicine, Yokohama, Japan, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY, Department of Cardiovascular Surgery, Shizuoka Medical Center, Shizuoka, Japan Abstract Disclosures Research Funding No funding received None. Background: Antibody-drug conjugates (ADCs) are attractive targeted agents in anticancer treatment due to their unique mechanism of action and reduced toxicity compared to other anti-cancer drugs. Yet little is still known about the adverse events profiles associated with ADCs. Methods: A systematic review was performed including randomized controlled trials (RCTs) of anticancer treatment that evaluated the efficacy of ADCs. PubMed and EMBASE were systematically searched for studies from January 1990 to December 2022. RCTs that were registered in ClinicalTrials.gov and had final reports of comprehensive adverse events were also included. We included studies for patients with both solid and hematologic tumors. The odds ratios (ORs) of treatment-related symptoms, and hematologic, hepatic, ocular, cardiovascular, renal, and respiratory toxicities for patients treated with ADCs and those without ADCs were examined. A random effects model was developed to estimate the pooled ORs of each adverse event associated with ADC use. Subgroup analyses were also performed based on the cancer type (solid tumors versus hematologic malignancy) and ADC regimen (ADC versus ADC plus chemotherapy). Results: 20 studies involving 10,075 patients (5,745 patients with ADC and 4,330 patients without ADC) were included. Among the included trials, 14 (70.0%) were trials for solid tumors and 6 (30.0%) were trials for hematological tumors. Among the included trials, ADC monotherapy was used in 15 (75.0%) experimental arms, and combination therapy of ADC with any other chemotherapy was used in 7 (35.0%). 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). Patients treated with ADCs had a significantly lower risk of all-grade febrile neutropenia (OR 0.46, 0.22-0.96), leukopenia (OR 0.47, 0.29-0.77), and neutropenia (OR 0.56, 0.31-1.01). Whereas, they had a higher risk of all-grade increased alanine aminotransferase (OR 2.51, 1.84-3.40), increased aspartate aminotransferase (OR 2.83, 2.04-3.93), cataract (OR 4.69, 1.86-11.81), blurry vision (OR 3.12, 1.02-9.55), pericardial effusion (OR 4.27, 2.71-6.72), and epistaxis (OR 2.45, 1.50-4.01). In the subgroup analysis, a similar toxicity profile was observed when comparing the solid tumors versus hematologic malignancy groups and the ADC versus ADC plus chemotherapy groups, except for hematologic adverse events, which showed an increased risk in patients with solid tumors and those treated with both chemotherapy and ADCs. Conclusions: This comprehensive profile of adverse events associated with ADC-based treatment shows increased treatment-related symptoms, hepatic, ocular, and cardiovascular toxicities although no increase of high-grade are seen.