Skin Care Regimen Cuts Toxicities of Combo NSCLC Therapy

An enhanced prophylactic regimen using widely available and easy-to-use agents significantly reduced the incidence and severity of dermatologic reactions associated with first-line amivantamab plus lazertinib in epidermal growth factor receptor (EGFR)-mutant advanced non–small cell lung cancer (NSCLC), early data from the COCOON trial showed.

Compared with standard-of-care dermatologic management, the enhanced prophylactic skin regimen led to significant reductions in grade 2 or higher dermatologic adverse events (AEs) and allowed more patients to stay on cancer treatment without dose interruption, reduction, or discontinuation.

“With the overall survival benefits seen with amivantamab plus lazertinib in MARIPOSA, we expect more patients to receive this combination, and the COCOON regimen should really be implemented in clinical practice to improve the patient experience,” said Nicolas Girard, MD, PhD, head of Medical Oncology, Institut Curie in Paris, France. 

In the MARIPOSA phase 3 trial, first-line treatment with amivantamab plus lazertinib significantly improved progression-free survival and overall survival compared with standard therapy in patients with EGFR-mutated NSCLC.

However, like other EGFR-targeted therapies, treatment with the combination causes cutaneous AEs, which are often treated reactively in clinical practice.

“Early management of dermatologic AEs is expected to allow patients to remain on treatment longer,” explained Girard, who presented results from the first interim analysis of COCOON at the European Lung Cancer Congress 2025.

The trial enrolled 201 patients with locally advanced or metastatic EGFR-mutant NSCLC receiving amivantamab/lazertinib therapy. Participants were randomly allocated to enhanced dermatologic management or standard-of-care dermatologic management.

Standard-of-care dermatologic management included general skin prophylaxis per local practice and reactive treatment, such as topical steroids and systemic antibiotics.

In contrast, enhanced management included an oral antibiotic (100 mg doxycycline or minocycline) administered twice daily for 12 weeks, followed by a topical antibiotic (1% clindamycin) applied to the scalp, an antibacterial wash (4% chlorhexidine) on the nails, and a ceramide-based moisturizer applied once daily to the body and face.

Girard explained that the interim analysis was preplanned for when approximately 70% of patients had completed week 12 assessments. This patient population included 138 patients: 70 in the enhanced dermatologic management group and 68 in the standard-of-care group. 

Baseline characteristics were well-balanced between the groups. The median duration of amivantamab/lazertinib treatment was 4.2 months in the enhanced management group and 4.1 months in the standard-of-care group.

“Demonstrating early success, the COCOON trial met its primary endpoint at the first interim analysis,” Girard told the conference attendees.

There was a twofold reduction in grade 2 or higher dermatologic AEs in the first 12 weeks — 39% in the enhanced management group vs 77% in the standard-of-care group (odds ratio [OR], 0.19; P < .0001).

Enhanced dermatologic management also led to a twofold reduction in grade 3 dermatologic AEs — 8.8% in the standard care group vs 4.3% in the enhanced group — and a threefold reduction in the number of patients who reported two or more different grade 2 or higher dermatologic AEs — 18% with the standard approach to 6% with the enhanced protocol.

“The benefit was consistent across all prespecified subgroups of patients,” Girard reported. 

He also noted that in the first 12 weeks, substantial reductions in grade 2 or higher dermatological AEs were observed on different body locations with enhanced care. This included a 65% reduction in facial and body dermatological AEs, a 70% reduction in scalp AEs, and a 25% reduction in nail toxicity.

Patients using the COCOON regimen had lower rates of amivantamab/lazertinib dose modifications due to dermatologic or any AE, as well as lower rates of discontinuations (11% vs 19%).

Girard added that COCOON is the first trial to report venous thromboembolism incidence in the setting of first-line amivantamab plus lazertinib treatment — and the incidence was low — 6% in the enhanced-care group vs 7% in the standard-of-care group.

The study is now fully enrolled with 201 patients, and additional results will be presented at upcoming congresses, the researcher said.

Proactive Not Reactive

Invited discussant Julien Mazieres, MD, PhD, pulmonologist and oncologist, and head of the Thoracic Oncology Program at Toulouse Cancer Institute in Toulouse, France, said the COCOON trial is a “very smart trial” trying to address the dermatologic toxicity of this regimen and find a prophylactic regimen to prevent it instead of taking a “reactive” approach.

While the results are “clearly positive,” 39% of patients using the enhanced prophylactic regimen still had grade 2 or higher dermatologic AEs — which is “still high, with a quality-of-life impact,” Mazieres said.

However, “very importantly, participants using the COCOON management had lower rates of amivantamab and lazertinib discontinuation,” he noted.

Another caveat, said Mazieres, is that it’s unclear exactly how patients in the standard-of-care group were treated as “we don’t have the details of the standard dermatologic management.”

In addition, the antibiotics used in the regimen do have some side effects, and they were given for 12 weeks. Some research has suggested that they shouldn’t be given for more than 6 weeks because they may induce resistance, Mazieres noted.

Overall, however, he said the regimen is “good” but may need “some adaptation.”

The COCOON trial is funded by Johnson & Johnson. Girard had disclosed relationships with Johnson & Johnson and other pharmaceutical companies. Mazieres had disclosed relationships with Roche, AstraZeneca, Pierre Fabre, Takeda, and other pharmaceutical companies.