Panelists discuss how managing common toxicities in combination therapies requires specific strategies including dose reductions and growth factor support for neutropenia with trifluridine/tipiracil, antihypertensive management for blood pressure elevations across different agents, and careful patient selection considering contraindications such as previous pelvic radiation (GI perforation risk), cardiac conditions, anticoagulation therapy (hemorrhage risk), hepatic impairment, advanced age, and complex pill burden management, emphasizing the importance of multidisciplinary care and selecting conscientious patients capable of adhering to precise dosing requirements.