Emetogenicity of Antibody-Drug Conjugates (ADCs) in Solid Tumors with a Focus on Trastuzumab Deruxtecan: Insights from an Italian Expert Panel

Simple Summary Four antibody-drug conjugates (ADCs) are approved for the treatment of solid tumors, improving the therapeutic index. Despite their high selectivity, nausea and vomiting are the most frequently observed side effects. A deeper understanding of the potential risk for nausea and vomiting is crucial, as they can affect patients' quality of life and treatment adherence. Prophylaxis with the potential combination of antiemetic therapy with complementary non-pharmacological approaches are even more important, considering that ADC therapies are generally given continuously until disease progression or the occurrence of toxicities. In the past decade, nine antibody-drug conjugates (ADCs) have been approved for the treatment of various tumors, four of which specifically for solid malignancies. ADCs deliver the cytotoxic payload to the cancer site, thereby improving chemotherapy efficacy while reducing systemic drug exposure and toxicity. With their high selectivity, ADCs are associated with a manageable side-effect profile, with nausea and vomiting being among the most frequent toxicities, although this may vary according to the respective ADC and the associated payload. Information about the emetic risk of the new ADC compounds is limited. Three virtual focus groups of Italian oncologists were held to raise awareness on the importance of an antiemetic prophylaxis regimen to prevent and mitigate ADC-associated emesis and its sequelae. After reviewing published evidence and guidelines, the three expert panels shared their experience on the early use of ADCs gained through the participation in specific clinical trials and their clinical practice. The following issues were discussed: antiemetic therapy during trastuzumab deruxtecan treatment, with a protocol adopted at the San Raffaele Hospital (Milan, Italy); the use of steroids; the management of anticipatory nausea during trastuzumab deruxtecan therapy; nutritional counselling; and effective doctor-patient communication. The experts acknowledged that recommendations should be drug-specific, and formulated opinion-based advice intended to guide physicians in their daily practice until further evidence emerges.