Pancreatic cancer hope rises as KRAS pill extends survival

Pancreatic cancer has long carried some of the bleakest odds in oncology, but a KRAS-targeting pill called daraxonrasib is showing results that could change how clinicians talk about the disease—while researchers push toward earlier detection, smarter screenin

For years, pancreatic cancer has felt like a diagnosis that arrives too late. The cancer can grow undetected for years, and by the time most people realize something is wrong, the prognosis is often grim.

Nearly 90 percent of patients die within the first five years of their diagnosis. Even as other cancers saw their mortality rates drop in recent years, pancreatic cancer’s death rate increased slightly from 1999 to 2020.

In the 1980s, scientists identified a gene—KRAS—that appeared pivotal to the uncontrolled cell growth driving the disease. But clinical trials repeatedly failed, and Dr. Anirban Maitra. director of NYU Langone’s Laura and Isaac Perlmutter Cancer Center and a longtime pancreatic cancer researcher. said pharmaceutical companies came to see pancreatic cancer as a “graveyard” for future drug development. He also said experts feared the gene was, in effect, “undruggable.”.

That long-held sense of being stuck is starting to shift.

A group of researchers is preparing to publish results from a clinical trial already reported in The New York Times. and the findings center on a KRAS-targeting pill called daraxonrasib. Among patients with metastatic pancreatic cancer who had already tried chemotherapy. the pill roughly doubled survival—raising it from seven months to 13 on average.

“For the first time, there is some optimism in this disease,” Maitra told me. “Oncologists who have been treating this cancer for decades have always been so pessimistic about the fact that so many trials have failed. These patients, unfortunately, live for a few months and die. But now we finally have the foundation on which to build.”.

It’s not a cure, and researchers stress that progress now depends on more than a single breakthrough. What lies ahead. they say. is the harder work of improving the full spectrum of care: identifying who is at risk. detecting the disease early. and building more effective treatments that offer patients years—not just months.

Doctors are getting better at figuring out who’s at risk

Part of the reason pancreatic cancer is so hard to catch is physical, not abstract. The pancreas is buried deep in the abdomen, and symptoms can be absent while the disease grows.

Maitra said the outlook improves when clinicians can target surveillance to people most likely to develop it. But he also said awareness is uneven. Many people. and even doctors. may not know what to look for. and pancreatic cancer has often lacked the kind of public attention that breast cancer—or even colon cancer—has received.

Pancreatic cancer accounts for about 3 percent of all cancer cases but more than 8 percent of cancer deaths, about 39,000 every year.

Smoking, age, and obesity are considered risk factors, but pancreatic cancer shares those with many other cancers. One risk factor Maitra highlighted is the sudden onset of adult diabetes, especially when accompanied by weight loss.

“If you’re like a 65-year-old and you’re presenting with new-onset diabetes and you just lost 10 pounds. I would be very worried about that person. I’d make sure I get some tests done on that person,” Maitra said. “Awareness is so important.” He clarified that most new-onset diabetes in an adult is just that. and isn’t a reason to panic. Still, he said the connection should be understood by more people and more health care providers.

New artificial intelligence programs could also help doctors spot higher-risk patients earlier. Maitra said hospitals are starting to experiment with scanning electronic health records or genetic samples and then singling out patients who may be at higher risk based on their medical history or the presence of certain genes associated with a greater chance of developing pancreatic cancer. including BRCA2.

Clinicians have better tools for detecting pancreatic cancer early

Once doctors identify people at risk, the next step is surveillance—looking for the cancer’s development before it becomes harder to treat.

Blood tests, often called liquid biopsies, have attracted major investment and media attention. Some companies want to create tests that can search for multiple cancers from one sample. but for now. single-disease versions have shown promising results. Maitra pointed to a test developed by Oregon Health & Science University that showed an 85 percent accuracy rate diagnosing early-stage pancreatic cancer when used alongside an existing antigen test.

AI is also entering the imaging stage. Maitra said a recent study found an AI program developed by Mayo Clinic researchers that examined routine abdominal CT scans and spotted pancreatic cancer at nearly double the detection rate of two human radiologists—finding the disease up to three years before a normal clinical diagnosis.

“This is where AI can really help because they can pick out subtle patterns that the human eye can miss,” Maitra said.

Scientists are developing better pancreatic cancer treatments

After detection comes treatment, and Maitra said options are improving.

He said the best current treatment remains surgical removal plus therapy, with better outcomes when tumors are smaller. Early detection matters because it can keep the cancer from having more time to metastasize and spread.

Even after surgery, the cancer can come back. Maitra said new vaccines are showing promise in preventing recurrence. He cited small preliminary studies identifying multiple vaccine candidates that allowed patients to live longer without relapse and survive overall longer than historical norms.

For patients facing the most dire scenario—when cancer can’t be removed by surgery—that is where KRAS-targeting drugs could matter most.

To simplify the science. Maitra described KRAS as a “greasy ball” that. for a long time. no drug molecules were able to attach to. He said Kevan Shokat. a scientist at the University of California San Francisco. figured out how to make a molecule attach to KRAS in 2013. Around the same time, Greg Verdine at Harvard University was working on a molecular “glue” that could disable KRAS. The new drugs. Maitra said. build on that research to deliver a compound to the gene and slow the out-of-control cell growth that causes pancreatic cancer.

He suggested patients and clinicians think of daraxonrasib—one that appears likely to receive FDA approval—as “the ground floor” for this class of drugs. He noted that many people still do not respond or experience severe side effects. and that the drug stops working after a period of time as the body develops resistance. Still, he said other drugs combining different molecules to extend effectiveness are already in the pipeline.

In the future. Maitra said pancreatic cancer treatment could look like a coordinated plan rather than a single bet: early detection. surgical removal to eliminate the bulk of a tumor. and then vaccines and/or KRAS-based treatments to prevent recurrence. For people who can’t undergo surgery, he said combinations of vaccines and KRAS-targeting drugs could be used instead.

The work is far from finished. But after decades of disappointments, Maitra said there is real reason for hope.

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