A new topical gel has demonstrated significant efficacy in treating a common and painful side effect of colorectal cancer therapy, potentially improving treatment outcomes for thousands of patients. According to research presented at the American Association for Cancer Research (AACR) Annual Meeting 2025, LUT014 successfully reduced the severity of acneiform rash caused by epidermal growth factor receptor (EGFR) inhibitors.
The Phase II clinical trial, led by researchers at The University of Texas MD Anderson Cancer Center, showed that patients who applied the topical BRAF inhibitor experienced substantial relief compared to those using a placebo gel.
"We're really excited about this novel topical gel. Having a therapy with low side effects and high efficacy is critical for improving quality of life and cancer treatment continuation for these patients," said principal investigator Anisha Patel, MD, associate professor of Dermatology at MD Anderson. "This rash can have a high impact on patients' quality of life. Better control of the rash can lead to better control of the cancer and a better chance at significantly improving outcomes."
Understanding the Treatment Challenge
Approximately 75% of colorectal cancer patients receiving EGFR inhibitors such as cetuximab and panitumumab develop a painful acne-like skin rash, primarily affecting the head, neck, and upper trunk. This side effect frequently leads to treatment interruptions, dose reductions, or complete discontinuation of cancer therapy.
The skin toxicity occurs because EGFR inhibition blocks the MAPK pathway, disrupting normal skin cell function and triggering an inflammatory response. Until now, available treatments have primarily addressed symptoms rather than the underlying cause, providing only temporary relief.
LUT014 represents a breakthrough as the first therapy targeting the mechanism of the rash itself. The topical BRAF inhibitor reactivates the MAPK pathway in the skin without being absorbed into the bloodstream, ensuring it doesn't interfere with the cancer treatment's effectiveness.
Clinical Trial Results
The multicenter trial enrolled 118 colorectal cancer patients across 23 medical centers who had developed moderate to severe acneiform rashes while taking EGFR inhibitors. Participants were randomly assigned to receive either a 0.1% formulation of LUT014, a 0.03% formulation, or a placebo gel for 28 days.
Treatment success was defined as either a one-grade or greater reduction in rash severity or improvement in at least five skin-specific quality-of-life criteria. The results were compelling:
- 69% success rate with the 0.1% LUT014 formulation
- 47.5% success rate with the 0.03% LUT014 formulation
- 33% success rate with the placebo gel
"LUT014 gel improved acneiform rash in the majority of treated patients within a remarkably short time frame of 28 days," Patel noted. "We saw results within a week for many of the patients."
Safety Profile and Patient Experience
While patients receiving LUT014 reported some adverse events, including itchiness, burning sensation, skin redness, and stinging at the application site, most were grade 1 in severity. Only one patient in the 0.1% LUT014 arm experienced a grade 3 adverse event, compared to three in the placebo arm.
Importantly, these side effects were considered an improvement over the symptoms of the rash itself, with patients reporting better overall quality of life.
"These rashes typically are treated with antibiotics or topical steroids, but we're seeing people develop resistance to those with long-term use," Patel explained. "LUT014 is the first treatment to target the mechanism of the rash without being absorbed in the bloodstream, allowing us to effectively treat this unfortunate side effect without compromising tumor treatment."
Broader Implications
The successful management of treatment-related side effects represents a significant advancement in supportive cancer care. By allowing patients to continue their prescribed therapy without interruption, LUT014 could potentially improve long-term cancer outcomes.
A Phase III clinical trial is currently being planned to further evaluate the effectiveness of this treatment. Additionally, researchers believe LUT014 may have broader applications beyond colorectal cancer, as other cancer therapies in development also affect kinase pathways.
"This investigational topical BRAF inhibitor has the potential to not only improve quality of life for patients receiving EGFR-targeted therapy but also improve their cancer treatment compliance and potentially their tumor response," Patel concluded.
The study was funded by Lutris Pharma, the developer of LUT014. Dr. Patel has disclosed consulting relationships with several pharmaceutical companies, including Lutris Pharma, and research funding to MD Anderson from various sources including Lutris Pharma.
