EGFR-related skin AE rates drop with COCOON regimen

Interim data from the phase II COCOON trial demonstrate the potential of the COCOON dermatologic management (DM) regimen to significantly reduce the incidence and severity of dermatologic adverse events (dAEs) tied to amivantamab plus lazertinib treatment in patients with EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC).

“Demonstrating early success, COCOON met its primary endpoint at the first interim analysis,” said Dr Nicolas Girard from the Institut du Thorax Curie-Montsouris, Paris, France, at ELCC 2025.

In the first 12 weeks, COCOON DM halved the rates of grade ≥2 (38.6 percent vs 76.5 percent; odds ratio [OR], 0.19; p<0.0001) and grade 3 (4.3 percent vs 8.8 percent) dAEs vs standard-of-care (SoC) DM.

The benefit with the enhanced regimen vs SoC was consistent across all subgroups, with the most profound effects among those weighing ≥80 kg (OR, 0.07), in men (OR, 0.08), and in patients aged ≥65 years (OR, 011). [ELCC 2025, abstract 10MO]

Adherence to the investigational regimen also led to a threefold reduction in the proportion of participants reporting ≥2 different grade ≥2 dAEs vs SoC DM use (6 percent vs 18 percent).

There were also substantial drops in the rates of grade ≥2 dAEs on various body locations with COCOON DM vs SoC DM, with ~70-percent reduction in scalp dAEs (9 percent vs 29 percent), about 65 percent in facial/body dAEs (excluding the scalp; 23 percent vs 62 percent), and 25 percent in paronychia (16 percent vs 21 percent).

The treatment effects subsequently led to a reduction in the rate of amivantamab or lazertinib discontinuation due to AEs with COCOON DM vs SoC DM (11 percent vs 19 percent), as the former allowed participants to remain on treatment for NSCLC. A similar pattern was seen for dose reduction (21 percent vs 31 percent).

No proactive therapy implemented

Evidence shows an association between EGFR-targeted therapies and dAEs, which are frequently treated reactively in the clinical practice setting. [Biosci Trends 2019;12:537-552; Lung Cancer 2022;173:116-123; Br J Dermatol 2016;175:1166-1174]

Based on the MARIPOSA study results, the FDA and EMA approved first-line amivantamab plus lazertinib for EGFRm advanced NSCLC. [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lazertinib-amivantamab-vmjw-non-small-lung-cancer; https://www.ema.europa.eu/en/medicines/human/EPAR/lazcluze, accessed 6 May 2025]

“[This combination] significantly improved overall survival for these patients. However, no proactive therapeutic management is implemented to mitigate the side effects of this combination,” underscored Girard.

In MARIPOSA, the first onset of dAEs occurred within the first 4 months of treatment. [ELCC 2025, abstract 4O]  “Early management of dAEs is expected to allow more patients to remain on treatment longer with amivantamab plus lazertinib,” he said.

The team set out to evaluate a simple prophylactic regimen for the prevention of moderate-to-severe EGFR-related dAEs. A total of 138 NSCLC patients (median age 62.5 years, 57 percent women) who received ≥1 dose of amivantamab plus lazertinib were randomized 1:1 to receive the COCOON DM or SoC DM for 12 months.

SoC DM comprised general skin prophylaxis according to local practice, which is mostly restricted to reactive treatments, such as systemic antibiotics and topical corticosteroids.

In the COCOON DM group, participants were given prophylactic antibiotics such as oral doxycycline or minocycline 100 mg BID (weeks 1–12) and 1% topical clindamycin lotion QD for the scalp (weeks 13–52). Other agents included are 4% chlorhexidine for nail cleaning and a noncomedogenic ceramide-based moisturizer for the face and body for long-acting skin hydration; both were to be used daily for 12 months.

“The prophylactic COCOON DM regimen, with widely available and easy-to-use agents, should be implemented in clinical practice to improve [patient outcomes],” Girard concluded.