COCOON DM Reduces Skin AEs With Ami/Laz for NSCLC

Byoung Chul Cho, MD, PhD, medical oncologist at Yonsei Cancer Center in the Republic of Korea, discusses the COCOON global study presented at the IASLC 2025 World Conference on Lung Cancer.

The COCOON study was conducted to determine if an enhanced dermatology management strategy, known as COCOON DM, could reduce skin-related adverse effects (AEs) in patients receiving first-line amivantamab (Rybrevant) plus lazertinib (Leclaza) for EGFR-mutant lung cancer.

This combination therapy was used because, as demonstrated in the MARIPOSA study, it significantly improves progression-free survival (PFS) and overall survival (OS) compared with osimertinib (Tagrisso). However, mitigation strategies for the dermatologic AEs associated with these agents were not evaluated. This analysis of the COCOON study included data from the fully enrolled (n = 201) cohort.

COCOON enrolled adult patients with histologically or cytologically confirmed locally advanced or metastatic NSCLC with EGFR ex19del or L858R, who were treatment naive and had an ECOG performance status score of 0 or 1. The study's primary end point was the rate of grade 2 or higher dermatologic AEs during the first 12 weeks.

The COCOON DM treatment was composed of oral doxycycline or minocycline for weeks 1 to 12 followed by topical clindamycin lotion of scalp for weeks 13 to 52. Chlorhexidine on nails and a ceramide-based moisturizer on body and face were used throughout study treatment. The standard-of-care DM regimen included general skin prophylaxis per local practice and reactive treatment (eg topical corticosteroids and systemic antibiotics).

The study successfully met this end point, showing a significant reduction in these AEs with COCOON DM compared with standard care (42% vs 75%; OR, 0.24; 95% CI, 0.13–0.45; P <.0001). This benefit was consistent across various skin sites and was maintained at 6 months.

The investigator-assessed overall response rate was 82% (95% CI, 73%–89%) in the COCOON DM arm and 75% (95% CI, 65%–83%) in the standard-of-care DM arm.

However, the incidence of paronychia was comparable between arms in the first 12 weeks of treatment.

REFERENCE:

Cho BC, Li W, Spira AI, et al. Enhanced vs Standard Dermatologic Management with Amivantamab-Lazertinib in EGFRm Advanced NSCLC: the COCOON Global RCT. Presented at: IASLC 2025 World Conference on Lung Cancer; September 5–9, 2025; Barcelona, Spain.