Due to fedratinib's significant GI side effect profile and the logistical difficulty of measuring thiamine levels, clinicians should proactively provide patients with thiamine supplements, anti-emetics, and anti-diarrheal therapies. Instructing patients to take the drug with food can also help mitigate GI toxicity.

Drawing lessons from T-DXD, experts treat newer exatecan-payload ADCs like RDXD as highly emetogenic from the first dose. Instead of a 'wait and see' approach, they recommend aggressive premedication with a triple-drug antiemetic regimen to prevent nausea and maintain quality of life.

To manage the acute GI toxicity of T-DXd, a preemptive three-drug antiemetic combination is recommended. Completely preventing nausea and vomiting is crucial not just for comfort, but for mitigating patient anxiety around chemotherapy and ensuring they can remain on this long-term treatment.

Nausea with TDXD is severe enough that the drug is now considered highly emetogenic. The standard of care is a prophylactic three-drug antiemetic regimen (NK1 antagonist, 5HT3 antagonist, and dexamethasone). Waiting for nausea to occur before treating is a clinical error; prevention is paramount.

The HORIZON-GEA-01 trial for zanidatumab in gastric cancer mandated prophylactic loperamide (4mg BID) for all patients. This was necessary to manage the high rates of diarrhea (up to 80% of patients), a significant GI toxicity associated with the drug's mechanism of action.

New targeted therapies like Zanidatamab and Zolbetuximab show great promise but cause significant side effects like diarrhea and nausea. Their successful clinical adoption hinges on proactive management using detailed guidelines and prophylactic medications, as toxicity can be severe enough to force treatment discontinuation despite the drug's efficacy.

Clinicians are finding that forgoing the standard 800mg loading dose of zolbituximab and starting directly with the 600mg maintenance dose appears to mitigate acute gastrointestinal toxicity, particularly gastritis. This practical adjustment is being formally studied but is already used in practice to improve patient experience.

Managing side effects of antibody-drug conjugates is not one-size-fits-all. Sazetuzumab-govatecan requires managing GI issues, while Datopotamab-deruxtecan has unique risks like ophthalmologic problems and ILD, necessitating pre-treatment specialist evaluation. Proactive patient education and tailored mitigation are key to maintaining treatment continuity and efficacy.

Severe nausea from the Claudin-18.2 antibody zolbetuximab dropped from ~20% in early trials to zero in a recent study. This was achieved not by changing the drug, but by clinicians learning and applying more effective proactive antiemetic strategies, demonstrating the power of evolving supportive care.