Daraxonrasib: What To Know About Common Side Effects

The new KRAS drug daraxonrasib generated great excitement among patients, but one of the first things people noticed was a startling red rash.

Former United States Senator Ben Sasse appeared on a podcast in April 2026 to tell the world how he was coping with stage IV pancreatic cancer. At the time of his diagnosis—December 2025—he was told he had about three months to live. But Sasse entered a clinical trial of Revolution Medicines’ KRAS inhibitor daraxonrasib. Thanks to this drug, his tumors shrank dramatically and he had significantly less pain. Sasse was also incredibly candid about the difficulty caused by one particular side effect of the drug.

Sasse’s face, as shown in publicly available images was, to put it bluntly, a mess. Red, raw, bleeding, and oozing pustules covered most of his face and some of his scalp. Sasse referred to the rash as “nuclear,” while simultaneously lauding daraxonrasib as a game changer.

Although daraxonrasib is not a cure for pancreatic cancer, results of the RASolute 302 trial showed the drug nearly doubled overall survival among patients with metastatic disease who have failed first-line treatment. And like all drugs, even the lowly aspirin, it comes with its own set of side effects.

The Skin You’re In

First, the good news. According to study results, all patients receiving daraxonrasib (and 97.7 percent receiving chemotherapy) had side effects related to the treatment. The most common side effects leading to dose reduction with daraxonrasib were rash and oral swelling and sores. However, daraxonrasib outperformed standard chemotherapies in terms of tolerability. Side effects leading to dose reductions were much less common in the daraxonrasib group, occurring in 36.1 percent of the patients versus 57.5 percent of those on chemotherapy. The most serious side effects occurred in 10.8 percent of those taking daraxonrasib versus 18.7 percent of those on chemotherapy.

Now, the not-so-good news. Almost all of the study participants taking daraxonrasib experienced an acne-like skin rash. The rash spans a spectrum from mild annoyance to full-blown misery in its most severe form. “If a patient is taking daraxonrasib it’s absolutely fair to say they have a good chance of getting a rash, and severity is really dependent on dosage and length of time on the drug,” explains oncodermatologist Ian W. Tattersall, M.D., Ph.D., of NYU Langone Health (New York). Oncodermatology is a relatively new subspecialty, in which dermatologists work in tandem with an oncology care team to help mitigate cancer treatment side effects that wreak havoc with the hair, skin, or nails. Tattersall has worked with many patients who were part of the daraxonrasib clinical trial.

“KRAS inhibitors are a new class of drugs so we are still figuring out how to best manage their toxicities,” he says. “Most of our experience with this type of rash comes from what we’ve learned from EGFR inhibitors.”

Indeed, targeting the EGFR (Epidermal Growth Factor Receptor) pathway leads to a skin rash because EGFR is found in healthy cells as well as malignant cells. “When you block the receptor normal growth and healing is disrupted, that can lead to inflammation,” Tattersall notes.  

Daraxonrasib works on the RAS signaling pathway, which is downstream of the EGFR signaling pathway. “As a targeted therapy it (daraxonrasib) is designed to block the mutated RAS proteins that are driving tumor growth and spread,” he says, “but it also disrupts healthy cells that rely on RAS signaling for normal growth, maintenance, and healing. Once the balance of normal cells in the pathway is disrupted, so is the renewal of normal skin cells. The skin has a tough time healing and maintaining itself.”

The rash closely resembles a bad case of acne, and most patients have milder cases. But a minority of patients have a more severe toxicity, with more widespread erosion and bleeding. “In my experience, and as shown in the study, most cases of skin rashes are mild and very manageable. It’s a small percentage that have grade 3 (severe) or greater skin side effects,” Tattersall says.

He adds, “But I don’t want to minimize how miserable that more severe skin rash can be if not properly managed. Skin rashes, really of any type, can isolate people because they become embarrassed and they don’t want to be seen. And if it is more severe, it can really hurt. I have had a few patients who have come pretty close to quitting the trial because of the severity of their rash.”

Upfront Management

Fortunately, none of those patients dropped out. The key is proper upfront management.

“What we really focus on is being proactive in trying to prevent a more serious rash if possible, and that should start on day one,” Tattersall explains. That strategy translates to prevention, topical treatments, antibiotics, and sun protection.

“Oral antibiotics like doxycycline, used upfront and taken twice a day, can be very beneficial,” he says. Patients may also be prescribed steroid creams like hydrocortisone, used for the face, and triamcinolone, for other rash locations. Moisturizing is also key, and patients are generally advised to use a bland emollient cream all over the body to prevent cracked skin. Sun protection is vital. “I cannot emphasize enough how important sun protection is for everyone, but especially for these patients who become very photosensitive because of the drug,” Tattersall continues, adding that protective clothing and a mineral-based sunscreen used daily can go a long way in keeping patients comfortable.

If the rash escalates, doctors may prescribe stronger topical or oral treatments. Dose modification or a temporary break from daraxonrasib may also be necessary for a short period of time to allow the skin to heal.

Managing Stomatitis

Stomatitis, or oral mucositis, is inflammation in the mucous membranes that line the mouth or lips. And it is a common cancer treatment side effect. The pain varies, but it can affect eating and drinking. Steroid mouth rinses or a compounded rinse dubbed “magic mouthwash” may be prescribed.

This “magic” rinse can include an antacid to coat mouth sores and to help the rinse adhere to the mouth lining. It may also include an antihistamine to mitigate swelling, a corticosteroid to reduce inflammation, and an antifungal or antibiotic to prevent secondary infections.

Doctors advise being kind to your mouth with gentle cleansing, avoiding alcohol, frequent salt rinses, and even over-the-counter numbing agents.

The Most Important Thing to Do

As more people have access to daraxonrasib through the FDA’s Expanded Access Program and potentially its FDA approval in the next few months, doctors will learn more about the drug’s side effects. “We are good at treating things now and we will only get better,” Tattersall says. “It appears that the company (Revolution Medicines) is also committed to learning more and getting information out to people. This drug has really improved the outlook for metastatic pancreatic cancer and it’s exciting that more people will have access. We all want to make sure that quality of life is also improved because quality of life is really an important factor in cancer treatment.”

The single most important piece of advice Tattersall has is to have a plan. “If you are going on daraxonrasib, ask your team what the plan is for side effects, especially skin rash,” he adds. “Ask if you are going to get prophylactic treatment. Ask who is in charge of managing your side effects. Ask if you will see a dermatologist or will your team consult with a dermatologist. Ask who is your main point of contact.

“The last thing any of us wants is to see is a patient stop taking this drug that extends life because a side effect like a rash isn’t properly managed.”