The Impact of SKIPirr and COCOON Protocols on Amivantamab Toxicities

The panel continued by discussing how toxicity profiles play a critical role in determining whether to use amivantamab/lazertinib in the frontline setting or reserve it for later lines (e.g.eg, in MARIPOSA-2). Dr.Helena Yu, MD, highlighted that while amivantamab is an active drug and will be used in practice, its sideadverse effects are unique—notably rash, infusion reactions, and edema. These can significantly impact quality of life, especially for patients sensitive to visible or chronic symptoms. In contrast, certain chemotherapy-related toxicities (e.g.eg, kidney issues with pemetrexed) may sway decisions in other directions, making personalization essential.

The COCOON regimen, which includes prophylactic strategies likesuch as antibiotics, topical agents, and premedication, has been implemented by some centers to mitigate amivantamab-related sideadverse effects, particularly rash and infusion reactions. Dr.Yu noted it can be effective but is also intensive, requiring highly motivated patients and well-coordinated care teams. Despite these efforts, some lower-grade but chronic toxicities—likesuch as hypoalbuminemia and leg edema—remain difficult to resolve and continue to burden patients over time.

Dr.Zosia Piotrowska, MD, MHS, emphasized that managing these toxicities is a team-wide effort. It requires not just physicians but also nurses, advanced practice providers, triage staff, and patient educators to coordinate education, early symptom management, and supportive care. With more clinicians using amivantamab in first- or second-line settings, this learning curve will affect everyone involved. She stressed that structured patient education materials, clear triage protocols, and close follow-up are essential to successfully integrate amivantamab-based therapies into broader practice, regardless of line of use.