COCOON trial

Prof Christophe Dooms and prof Mariana Brandao discussed the updated results of the COCOON trial. The study addresses an underexplored but clinically significant area: supportive care in patients receiving amivantamab plus lazertinib, a regimen associated with substantial dermatologic toxicity. The trial is particularly relevant in light of the MARIPOSA phase III results, recently published in the New England Journal of Medicine, demonstrating a clear overall survival benefit of amivantamab–lazertinib over osimertinib, with 3-year survival rates of 60% and 51%, respectively. However, this dual EGFR blockade is accompanied by high rates of cutaneous adverse events, underscoring the need for preventive strategies.

The COCOON trial is a randomised phase II study enrolling 200 patients, divided equally between standard dermatologic care and enhanced prophylactic dermatologic management. The latter regimen included oral antibiotics twice daily, daily topical antibiotics for face, scalp, and hair, full-body moisturizers applied once daily after showering, and chlorhexidine for nails. The primary endpoint was the incidence of grade ≥2 skin toxicity within the first 12 weeks, with secondary endpoints assessing quality of life and treatment adherence.

Results from the first 12 weeks demonstrated a marked reduction in skin toxicities with enhanced management. Overall rash incidence (grade ≥2) declined from 62% under standard care to 27% with prophylaxis. Specific reductions were observed at key sites: facial rash decreased from 48% to 15%, scalp rash from 25% to 10%, and rash elsewhere from 44% to 20%. By contrast, the incidence of grade ≥2 paronychia was unaffected (23% vs. 21%). Importantly, improved toxicity control translated into a reduction in treatment interruptions, observed in 10% of patients in the prophylaxis arm versus 23% in the control arm.

Patient-reported outcomes mirrored these findings. Using the Skin Index-16 tool, a significant improvement in dermatology-related quality of life was observed, consistent with the reduction in rash severity. These benefits are of particular relevance given the psychosocial burden of visible toxicities affecting the face and scalp. Nevertheless, data remain immature: over 70% of patients are still on treatment, and long-term effects of prophylactic strategies on adherence and outcomes are not yet known.

The clinical applicability of these findings is promising. The regimen is simple, easily implementable, and could be integrated into routine care, though patient education will be crucial to ensure adherence. Importantly, multidisciplinary collaboration with dermatologists is required to optimise management, particularly for paronychia and other localised complications. Furthermore, these strategies may have broader relevance beyond EGFR-directed therapies, extending to other targeted or immunotherapy combinations that induce cutaneous toxicity.