Insights from COCOON: Prophylactic Dermatologic Management With Amivantamab + Lazertinib in Advanced NSCLC

Summary for Physicians: 1L Therapies for LA/M EGFR-Mutated NSCLC

Summary for Physicians: COCOON Study Findings Presented at European Lung Cancer Congress 2025

The COCOON study is a Phase 2, open-label, randomized clinical trial designed to evaluate the impact of enhanced dermatologic management on DAEs in patients with locally advanced or metastatic (LA/M) EGFR-mutated NSCLC receiving first-line treatment with amivantamab and lazertinib. The study specifically addresses the unmet need for effective management of skin-related toxicities associated with EGFR-targeted therapies, which can significantly affect patients' quality of life and treatment adherence.​

Study Arms and Regimens:

• Enhanced dermatologic management arm:
• Patients receive a proactive regimen comprising prophylactic antibiotics, comprehensive skin moisturization, and strategies to prevent paronychia (nail inflammation). This approach aims to minimize the occurrence and severity of DAEs during treatment.​
• Standard dermatologic management arm:
• Patients receive conventional care, which may include reactive treatments initiated after the onset of dermatologic toxicities.​

Primary End Point:

• Incidence of Grade 2 DAEs:
• The primary objective was to assess the incidence of Grade 2 DAEs within the first 12 weeks of treatment. The enhanced management strategy demonstrated a statistically significant and clinically meaningful reduction in the occurrence of these adverse events compared with standard care. ​

Secondary End Points:

• Severity and frequency of dermatologic toxicities:
• Enhanced management resulted in a lower severity and frequency of DAEs, contributing to improved patient comfort and potentially better treatment adherence.​
• Quality-of-life assessments:
• Patients in the enhanced management arm reported improved quality-of-life metrics, likely due to reduced DAEs.​
• Treatment compliance:
• The proactive dermatologic care approach was associated with higher treatment adherence rates, as patients experienced fewer treatment interruptions related to skin toxicities.​

Addressing Unmet Needs in Clinical Practice:

The COCOON study directly addresses a significant unmet need by providing evidence-based strategies to manage dermatologic toxicities associated with EGFR-targeted therapies. By implementing enhanced dermatologic care, health care providers can offer patients a more tolerable treatment experience, potentially leading to:​

• Improved patient quality of life: Effective management of skin-related adverse effects enhances daily functioning and emotional well-being.​
• Increased treatment adherence: Minimizing AEs supports consistent therapy continuation, which may improve clinical outcomes.​
• Optimized clinical outcomes: Addressing dermatologic toxicities proactively may reduce the need for dose modifications or interruptions, ensuring patients receive the full benefit of their prescribed therapy.​

Incorporating enhanced dermatologic management into routine care for patients undergoing treatment with amivantamab and lazertinib represents a meaningful advancement in supportive oncology care, aligning with the goal of personalized medicine that considers both the efficacy and tolerability of cancer therapies.