Topical BRAF inhibitor relieves EGFR-induced acneiform eruption

LUT014 gel, a novel, small-molecule, topical formulation of a BRAF inhibitor, relieves acneiform rash toxicities from anti-EGFR therapies, findings from a phase II study suggest.

“Up to 90 percent of patients treated with anti-EGFR therapies experience papulopustular acneiform rash, leading to impaired quality of life (QoL) and suboptimal adherence to anti-EGFR therapies,” said Dr Anisha Patel from The University of Texas MD Anderson Cancer Center, Houston, Texas, US, at AACR 2025.

In one study, three quarters of participants on EGFR inhibitors had a rash, shared Patel. “And of these patients, two-thirds had dose impact on their cancer therapy because of the rash alone.”

The standard treatments for acneiform eruption are oral tetracyclines, topical steroids, and oral retinoids, but none have been approved by regulatory bodies. “Hence, there is still an unmet need for advanced management and regulatory approval,” Patel said.

The investigators evaluated 118 patients with metastatic colorectal cancer (CRC) who developed grade 2 or noninfected grade 3 acneiform lesions while on treatment with an EGFR-targeted antibody (eg, cetuximab or panitumumab). Participants were randomized 1:1:1 to LUT014 gel 0.1% (high-dose) or 0.03% (low-dose) or a placebo gel. They were instructed to apply the gel to the rash daily for 28 days. [AACR 2025, abstract CT018]

In the intent-to-treat analysis, nearly 70 percent of participants on the high-dose formulation experienced treatment success. This was more than double the rate reported for placebo (33 percent; p=0.0015). The low-dose arm also showed a trend towards clinical benefit but fell short of statistical significance when compared with placebo (47.5 percent vs 33 percent; p=0.12).

The per-protocol* analysis yielded similarly positive results for high-dose (76 percent vs 34.5 percent; p=0.002) and low-dose LUT014 (59 percent vs 34.5 percent; p=0.07).

“[Of note,] even the perioral areas, which can be quite difficult to treat because of irritation and treatment resistance, responded well [to treatment]. Patients who had seborrheic dermatitis-acneiform eruption overlap also had a response,” Patel shared.

Treatment success was a composite endpoint that captured either objective or subjective improvement, Patel explained. Treatment success was defined as a one-grade improvement in skin toxicity as per CTCAE** or a five-point improvement in patient-reported outcomes (ie, first 13 [skin-directed] of the 18 questions in the FACT-EGFRI-18 HRQoL*** questionnaire).

Both LUT014 formulations led to fewer interruptions of anti-EGFR therapy due to acneiform rash compared with placebo (n=4 vs 11; p=0.04 [high-dose] and n=5 vs 11; p=0.09 [low-dose]).

Adverse events associated with LUT014 were minimal, with most patients reporting pruritus or skin irritation.

Takeaways

Taken together, LUT014 0.1 gel provides statistically significant benefit over placebo for the treatment of acneiform rash associated with cetuximab or panitumumab treatment in patients with advanced CRC. There were no significant toxicities reported with the experimental agent relative to placebo, and the rates of anti-EGFR therapy interruption were low.

“What makes this inhibitor so unique is its mechanism of action,” said Patel. “As opposed to most of the therapies we have for EGFR-induced acneiform eruptions, which are symptom directed, the [LUT014 gel] actually works on the mechanism of the rash.”

“This investigational topical BRAF inhibitor has the potential to not only improve QoL for patients receiving EGFR-targeted therapy but also improve their cancer treatment compliance and potentially their tumour response,” Patel noted in a press release.