Abstract
Simple SummaryFour 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.
Highlights
Antibody-drug conjugates (ADCs) are potent targeted therapies with proven efficacy across a variety of hematological and solid malignancies [1–4]
The recent ASCENT trial [26], conducted in metastatic triple-negative breast cancer patients, further supports the use of antiemetic prophylaxis, it remains to be defined whether the optimal antiemetic regimen requires two or three drugs, considering that the investigators were allowed to choose between the two options and that the data on this side-effect control, according to the regimen used, are missing
According to the direct experience of most of the experts with trastuzumab-deruxtecan (T-DXd) and the ASCO and NCCN recommendations, the experts agreed that T-DXd is the only antibody-drug conjugates (ADCs) for which the need for prophylaxis of chemotherapy-induced nausea and vomiting could be discussed in depth
Summary
Antibody-drug conjugates (ADCs) are potent targeted therapies with proven efficacy across a variety of hematological and solid malignancies [1–4]. There are three types of emesis, each one with particular characteristics that require specific antiemetic approaches: (i) acute emesis, which occurs within 24 h of administration; (ii) delayed emesis, which has been arbitrarily defined as emesis presenting more than 24 h after administration, and can persist for several days, even up to the subsequent cycle of treatment; (iii) anticipatory emesis, which occurs immediately before administration of the anti-cancer therapy in patients with prior experience of acute or delayed treatment-induced emesis. It is usually triggered by the sight and/or smell of the room where therapy is administered [13–15]. This classification is arbitrary and does not take into account individual risk factors for emesis, it represents a useful clinical reference framework for commonly used drugs and for new compounds
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