- Daraxonrasib doubles survival in advanced metastatic pancreatic cancer patients
- The drug targets the previously undruggable KRAS mutation in pancreatic cancer
- It improves quality of life by reducing pain and tumour size during treatment
Pancreatic cancer is one of the most severe, aggressive, and deadly forms of cancer with a high mortality rate. Research over the years indicates that pancreatic cancer is exceptionally difficult to detect early and is highly resistant to standard treatments. The severity of the disease is shaped by its subtle presentation, rapid progression, and biological characteristics, making it one of the leading causes of cancer-related deaths worldwide. However, a recent breakthrough can change the narrative in the coming years.
Daraxonrasib, a once-daily pill, has been found to double survival among patients with advanced metastatic pancreatic cancer. Presented at the 2026 Annual Meeting of the American Society of Clinical Oncology (ASCO) and published in the New England Journal of Medicine (NEJM), the findings are promising for improving pancreatic cancer treatment worldwide.
Dr. Shubham Pant, M.D., Anderson Cancer Center, Houston, a co-author of the study, calls Daraxonrasib the biggest pancreatic cancer breakthrough in the last 50 years. In a conversation with NDTV, Dr. Pant revealed how this drug targets the "undruggable" KRAS mutation in pancreatic cancer and doubles the survival while improving overall quality of life and treatment outcomes.
"The KRAS mutation was discovered about 40 years ago, and 90% of pancreatic cancers are driven by the KRAS mutation. It is considered undruggable. KRAS protein is like a shiny ball and you can't stick any agent to it. This drug is truly a breakthrough as it can target the undrugable," said Dr. Pant.
"For pancreatic cancer, we've done a lot of trials, and they've failed." How is daraxonrasib different from previous therapies
In contrast to previous targeted therapies that focused on particular KRAS subtypes, daraxonrasib functions as a multiselective inhibitor that can address a broader variety of RAS-driven tumours. Researchers speculate that this broader range of activity may account for its encouraging outcomes across various mutation types.
"When the first results came out, we just knew the top-line result, which was doubled overall survival. For pancreatic cancer, we've done a lot of trials, and they've failed. That means they have not shown any advantage. Even in the trials which have shown any advantage typically resulted in only a few weeks to months of improvement. And this drug doubled the survival. So it was truly remarkable when I saw it," added Dr. Pant.
Also read: Pancreatic Cancer Breakthrough: New Daily Pill Doubles Survival Time For Advanced Patients
What exactly is daraxonrasib?
Daraxonrasib belongs to a new class of medicines known as RAS(ON) inhibitors. The drug targets the active form of RAS proteins, which help drive tumour growth and survival.
"This drug is very unique. It's like a molecular glue."
Dr. Pant, an alumnus of Maulana Azad Medical College, New Delhi, explains how daraxonrasib functions in an Indian context. "Think about it (RAS proteins) as a light switch in the body, which is stuck in the on position like fevicol has bounded to the on position, you can't turn it off. This gives the cell a growth signal, and that's how it becomes cancerous. So what this drug does is it acts like Velcro, like a sticky piece, sticks to that switch and turns it off, leading to cancer cell death. That's what it does essentially. So it's a RAS(ON) inhibitor," he added.
"It's just remarkable because before any trials that we've done in pancreatic cancer have either failed, have not shown a benefit, or have shown a benefit of a few weeks to months. And this drug showed double the survival in these patients over chemotherapy," he mentioned.
Dr. Pant said that this targeted agent can be given to patients instead of chemotherapy.
Benefits beyond survival
Cancer diagnosis can be life-changing; subsequently, treatment can lead to significant emotional stress. The fear of the unknown, concerns about treatment efficacy, and anxiety about potential side effects can weigh heavily on patients and their families. The combination of physical, emotional, and practical challenges makes treatment a daunting experience for most cancer patients.
While survival rates are the main highlights of a cancer treatment, it is also essential to focus on the quality of life of patients during cancer treatment. This drug promises to improve both in individuals with pancreatic patents.
"Survival is just one thing, which is very important. But pancreatic cancer is a tough disease. Patients lose weight, they lose lean body mass, they have a lot of pain, and indigestion."
"What we saw in this trial was that the patient-related outcomes, called PROs, which means how much pain they have, all that dramatically improved on daraxonrasib. This is primarily because it shrunk the tumours. As a result, patients actually felt better while they were on the therapy, which you never hear. When we talk about cancer therapy, people say, Oh my God, it's gonna be terrible. One may have nausea, vomiting, or diarrhea."
"There were side effects associated with the drug. There's no question about that. However, the patients interestingly felt better because, again, the pain was controlled," explained Dr. Pant.
He further mentioned that the patients were taking fewer medicines for pain, which is very crucial for patients as it directly impacts quality of life.
Are there any side effects?
"Yes," but they were well tolerated during the trial, said Dr. Pant.
"The main side effect we saw with this drug is a rash in about 90% of patients. In 10 to 15% of patients, it can be a grade three rash. This means it can be over most of the body. But the side effects are manageable with adjustments and creams given to the patients," he said.
"We also gave some antibiotics to patients. We're learning more and more about how to treat this rash. Some patients can experience mouth sores, which are medically called stomatitis."
"Some patients can also get a little bit of diarrhea and nausea that can be associated with the drug also. But overall, fairly well tolerated," he added.
When will daraxonrasib reach patients?
"Right now, it's in America, it's with the FDA. The FDA has to give approval to it. They're obviously gonna look at the trial, we know the results, but we still need approval. So right now, we do not have that access to treat our patients with it. But hopefully, it'll get approved by the FDA. And so then we'll have access to this drug to give to our patients, at least in America," Dr. Pant answered.
Can it be combined with chemotherapy, immunotherapy, and surgeries to improve overall cancer treatment outcomes?
The researchers have already started a consecutive trial called RASolute 303. "So this was a 302 trial. We already started a trial called RASolute 303, which we are moving this drug to the frontline setting."
In RASolute 303, the researchers are randomising patients with Daraxonrasib as a single agent and in combination with a chemotherapy called Gem Nab-paclitaxel, which is a frequently used chemotherapy in pancreatic cancer treatment. "We are combining it, and we're moving to the frontline setting so that patients can get earlier benefit potentially to the drug, and then also combination therapies."
According to the Dr. Pant, this drug has the potential to benefit patients all around the globe. The fatality rate for pancreatic cancer is particularly high.
"It's probably in the top 10 cancers because it's a very tough disease, essentially. So we are hoping that when this drug is available, it is accessible globally," the expert said.
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