BACKGROUND: Antibody-drug conjugates (ADCs) are a class of treatment agents for cancer combining the relative selectivity of targeted treatment with the cytotoxicity of chemotherapy drugs. Over 100 ADCs are under evaluation in clinical trials worldwide, but only 5 had been approved by both the US Food and Drug Administration and the European Medicines Agency at the time of study conduct: brentuximab vedotin (BV), ado-trastuzumab emtansine (T-DM1), gemtuzumab ozogamicin (GO), inotuzumab ozogamicin (IO), and polatuzumab vedotin (PV).
OBJECTIVES: To identify the most common toxicities reported from phase 2-4 clinical trials or observational studies for the five mentioned ADCs.
METHODS: We searched PubMed and Embase in July 2019 for peer-reviewed, English-language articles published since 2015 that reported the toxicity of ADCs. We first identified the most commonly reported adverse events (AEs) (reported in at least 10% of patients in each study) and then calculated the median reported incidence for each AE and drug.
RESULTS: The literature search identified 357 unique publications. After reviewing titles and abstracts, we selected 58 articles for full-text review; 48 of these qualified for data extraction. Among the 48 selected studies, 18 (38%) reported AEs for BV, 15 (31%) for T-DM1, 7 (15%) for GO, 7 (15%) for IO, and 1 for PV (1%). Most included articles reported on both efficacy and safety; 40 reported on clinical trials (22 phase 2, 17 phase 3, and 1 phase 4), and 8 reported on observational studies. Of the 2 ADCs with more included studies, the median incidences of AEs of any grade were higher for BV than for T-DM1 for many AEs: anaemia (31% vs. 24%), neutropenia (32% vs. 13%), thrombocytopenia (57% vs. 29%), peripheral sensory neuropathy (23% vs. 13%), fatigue (40% vs 30%), nausea (40% vs. 36%), vomiting (26% vs. 18%), and diarrhoea (29% vs. 18%). On the other hand, median incidences were lower for BV than for T-DM1 for anorexia (18% vs. 21%), pyrexia (19% vs. 25%), myalgia (12% vs. 16%), and headache (14% vs. 27%). IO had higher median AE incidences than BV and T-DM1 for neutropenia (42%), thrombocytopenia (72%), fatigue (45%), nausea (49%), and pyrexia (32%). For GO, safety information was scarce; the median incidence was 45% for thrombocytopenia, 45% for increased aspartate aminotransferase, and 50% for fatigue. Finally, PV had the highest incidence of fatigue (60%) and diarrhoea (47%) based on a single study.
CONCLUSIONS: The five approved ADCs were found to have somewhat distinct safety profiles. Most studies, especially most observational studies, reported on BV and T-DM1, which have been in the market longer than the other ADCs.
