A novel topical formulation of a BRAF inhibitor significantly reduced acneiform rash associated with anti–epidermal growth factor receptor (EGFR) therapies in patients with colorectal cancer, a new study found.
This gel could improve treatment adherence, said Anisha B. Patel, MD, lead author of the phase 2 clinical trial, during her presentation of the results at the American Association for Cancer Research (AACR) Annual Meeting 2025.
The study found that LUT014 gel at 0.1% concentration demonstrated statistically significant improvement over placebo in reducing the severity of acneiform rash, a common side effect that often leads to interruption or discontinuation of life-extending cancer therapies.
“Up to 90% of patients treated with anti-EGFR therapies experience papulopustular acneiform eruption, leading to impaired quality of life and suboptimal adherence to the anti-EGFR therapies,” explained Patel during her presentation. In an earlier study, 75% of patients who were on monoclonal antibody EGFR inhibitors had a rash. “Of those patients with the rash, two thirds had a dose impact on their cancer therapy because of the rash alone.”
Mechanism of Action
During her talk, Patel, who is a dermatologist at MD Anderson Cancer Center, Houston, explained the scientific rationale behind investigating the use of LUT014 to mitigate skin rash caused by anti-EGFR therapies.
“What makes this inhibitor so unique is the mechanism of action as opposed to most of the therapies we have for EGFR inhibitor–induced acneiform eruption, which are symptom-directed. This formulation actually works on the mechanism of the rash,” Patel said.
During an interview with Medscape Medical News, Patel explained that EGFR inhibition in the skin leads to acneiform eruption.
“With topical BRAF inhibition, there is a paradoxical upregulation of the downstream MAP kinase pathway,” she said. “This reverses the effects of the EGFR inhibition in the skin only. Phase 1 trials showed no systemic absorption of the BRAF inhibitor.”
Previous dose-escalation phase 1 testing of LUT014, conducted in 10 patients with colorectal cancer experiencing grades 1-2 acneiform rash from EGFR inhibitors, showed no systemic absorption of the topical LUT014. LUT014 was well tolerated, with no dose-limiting toxicities.
Study Design
The double-blind, placebo-controlled trial enrolled 118 patients with metastatic colorectal cancer who were receiving cetuximab or panitumumab and had developed grade 2 or noninfected grade 3 acneiform lesions. Participants were randomly assigned 1:1:1 to receive either LUT014 0.1% gel, LUT014 0.03% gel, or placebo gel for 4 weeks.
The primary endpoint was treatment success, defined as either one Common Terminology Criteria for Adverse Events grade improvement in skin toxicity (investigator-assessed) or a 5-point improvement in patient-reported outcomes using the first 13 skin-directed questions of the FACT-EGFRI-18 health-related quality-of-life questionnaire.
Significant Clinical Benefit
In the intent-to-treat analysis, the high-dose LUT014 (0.1%) demonstrated a 74% success rate compared with 28% in the placebo group (P=.0001). The lower-dose formulation (0.03%) showed a 56% success rate (P=.021 vs pl