Balancing Efficacy and Tolerability: Expert Insights Into Tucatinib Triplet Therapy for HER2+  Breast Cancer

Clinical Brief: Toxicity Management with Tucatinib-Based Therapy

Key Themes:

• HER2CLIMB Regimen Adverse Effects: Most common toxicities stem from capecitabine (diarrhea, palmar-plantar erythrodysesthesia)
• Modified Dosing Strategies: Alternative capecitabine dosing schedules (1 week on/1 week off) and reduced starting doses (1000 mg twice daily) improve tolerability
• Financial Toxicity: Cost barriers with oral therapies can influence treatment decisions despite clinical appropriateness

Key Points for Physicians:

• Diarrhea rates are higher with tucatinib (80% vs 50%), requiring proactive management
• Focus patient education on the most common and impactful toxicities rather than covering all potential adverse effects
• Consider financial implications when prescribing oral therapies, particularly for Medicare patients
• Preventive strategies for palmar-plantar erythrodysesthesia include skin lubrication and, potentially, topical agents such as diclofenac gel

Notable Insights:

• Clinical trial dosing of capecitabine often exceeds what patients can tolerate in real-world practice
• Patient education should be targeted to the most likely adverse events rather than overwhelming patients with all potential adverse effects
• Medicare’s $2000 annual out-of-pocket cap still presents challenges when patients must pay substantial amounts up front

Clinical Significance:

Successful implementation of tucatinib-based therapy requires proactive toxicity management, appropriate dose modifications, and consideration of financial toxicity, highlighting the importance of personalized treatment approaches that balance efficacy with quality of life and accessibility.