Propylactic Strategies in Managing Dermatologic AEs with Amivantamab: Expert Insights from the COCOON Trial

Skin toxicities, especially scalp rashes, are a significant concern with certain EGFR inhibitors, including those used in newer regimens. The recent Cocoon trial specifically addressed this issue by developing a four-part prophylactic regimen aimed at preventing and managing these dermatologic side effects. This regimen includes oral antibiotics started from day one and continued for several months, alongside a clindamycin-containing topical cream or lotion to treat rash areas. Additionally, patients use a prophylactic treatment for nail toxicity, which can also be a major problem, and a ceramide-based lotion applied to the face and body to prevent further skin damage. The trial demonstrated a significant reduction in skin toxicity and improved patient quality of life, making it a practical and cost-effective strategy now being integrated into clinical practice alongside anticoagulation measures.

Incorporating this prophylactic skin care regimen alongside the previously discussed skipper regimen for infusion reactions has become a cornerstone in patient management, helping patients navigate the most challenging parts of treatment with better comfort and fewer complications. Despite the simplicity and low cost of these measures, it is crucial to ensure they are followed consistently. In community settings, where providers may not have access to the same resources or support teams as academic centers, education about the rationale behind prolonged antibiotic use and topical therapies is vital. Patients often hesitate to start preventive antibiotics or use lotions, particularly men, who may be reluctant to apply skincare products. Clear communication explaining how these strategies prevent severe side effects improves adherence and ultimately treatment success.

Overall, managing adverse events in frontline combination therapies requires a dual focus on educating both providers and patients. While the unique toxicity profiles of these regimens can be challenging, proactive and preventive care—backed by clinical evidence—enables safer, more tolerable treatment. As supportive care protocols evolve and awareness grows, clinicians are better equipped to help patients benefit fully from these advanced therapies, delivering optimal outcomes while minimizing discomfort and complications.