Reducing Skin Toxicities from EGFR Inhibitors with Topical BRAF Inhibitor Therapy

Area of Science:

• Oncology
• Dermatology
• Pharmacology

Background:

• Epidermal Growth Factor Receptor (EGFR) inhibitors are crucial cancer treatments but cause dose-limiting skin toxicities via MAPK pathway inhibition.
• BRAF inhibitors paradoxically activate the MAPK pathway downstream of EGFR, presenting a potential therapeutic strategy for these toxicities.

Purpose of the Study:

• To evaluate the safety and efficacy of topical BRAF inhibitor LUT014 in managing EGFR inhibitor-induced acneiform rash.
• To test the hypothesis that topical LUT014 can mitigate skin toxicities associated with EGFR inhibitor therapy.

Main Methods:

• A Phase I clinical trial involving ten patients with metastatic colorectal cancer experiencing acneiform rash from cetuximab or panitumumab.
• Patients were enrolled in three cohorts to receive topical LUT014 therapy.

Main Results:

• Topical LUT014 was well tolerated with no dose-limiting toxicities observed.
• Acneiform rash improved in 6 out of 10 patients, particularly those with grade 2 rash in lower dose cohorts.

Conclusions:

• Topical LUT014 demonstrates safety and efficacy in improving EGFR inhibitor-induced rash.
• This approach offers a localized treatment for skin toxicities, potentially allowing for continued EGFR inhibitor dosing.