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Breakthrough CINV requires adding or intensifying agents from a different pharmacologic class than those used for prophylaxis. Escalating olanzapine to 10 mg daily for 2–3 days is effective for refractory nausea (often harder to control than emesis) and can be combined with PRN dopamine antagonists (metoclopramide or prochlorperazine) for synergistic effect. Rotating or stacking 5-HT3 antagonists alone (Option A) offers limited benefit because serotonin pathways are already blocked and delayed-phase emesis is more substance P–mediated. Scopolamine (Option C) targets vestibular pathways and is not first-line for chemotherapy-related mechanisms. Promethazine alone (Option D) provides sedation but is inferior as monotherapy for breakthrough symptoms. APRN management includes correcting dehydration/electrolytes, assessing for mucositis or gastroparesis, reinforcing small frequent meals, and reviewing interacting meds (opioids, antibiotics). For future cycles, consider optimizing delayed-phase coverage (extend dexamethasone, scheduled olanzapine) or using alternative NK1 RA schedules. Document response and adverse effects (somnolence, orthostasis) and provide clear home rescue plans.