Experimental pill nearly doubles survival for advanced pancreatic cancer

For decades, pancreatic cancer has resisted the kind of targeted drug breakthroughs that transformed treatment for other malignancies. The disease kills more than 52,000 Americans each year, and those diagnosed rarely survive five years. The reasons are brutal: it spreads silently before detection, and the mutations driving it—particularly in a gene called KRAS—seemed locked away from pharmaceutical intervention. Researchers called KRAS undruggable. That assessment may have just changed.

A new pill called daraxonrasib, tested in a 500-patient clinical trial, nearly doubled survival time for people with advanced pancreatic cancer that had stopped responding to prior chemotherapy. Those who took the daily pill lived a median of 13.2 months, compared to 6.7 months for patients who received additional chemotherapy. The findings, published in the New England Journal of Medicine and presented at the American Society for Clinical Oncology meeting in Chicago on Sunday, represent the first drug to show a substantial survival advantage over chemotherapy for this population. The pill also produced fewer severe side effects and allowed patients to remain on treatment longer, with reports of less pain and better quality of life as their tumors shrank.

The breakthrough hinges on how the drug works. Daraxonrasib targets mutations in the KRAS gene family, which normally regulate cell growth but become cancer-driving when mutated. These KRAS mutations appear in more than 90 percent of pancreatic cancers. The problem was structural: the mutated proteins had a shape that made it nearly impossible for drugs to bind to them. Revolution Medicines, the company that developed daraxonrasib, solved this by using what amounts to a molecular glue—a chemical approach that allows the drug to stick to multiple KRAS subtypes and block their tumor-fueling activity.

Dr. Zev Wainberg of UCLA, who helped lead the study, called it "a very large step forward," though he was careful to note the drug does not cure cancer. Dr. Rachna Shroff of the University of Arizona Cancer Center, who was not involved in the research, described her reaction to the data more emotionally. "Having treated pancreatic cancer for 16 years, I actually started crying," she said, struck by how patients stayed on the treatment because it delivered "durable and meaningful benefit." Many patients continued using daraxonrasib even after the trial data was locked for analysis, suggesting the survival advantage may ultimately prove larger as follow-up continues.

The most common side effects were a rash—sometimes severe—and mouth sores. These were manageable enough that they did not drive most patients to stop taking the drug. The FDA is moving forward with expedited review of daraxonrasib and has already begun an expanded access program allowing patients who meet certain criteria to receive the experimental drug outside the trial. The program has generated intense demand; oncologists report being flooded with requests, partly fueled by public attention after former U.S. Senator Ben Sasse described on "60 Minutes" how the pill reduced his pain.

Dr. Brian Wolpin of Dana-Farber Cancer Institute, who presented the findings, said daraxonrasib should become "a new standard of care" for previously treated metastatic pancreatic cancer. But researchers are already looking beyond this population. The next phase will explore whether the drug works earlier in the disease course, and whether tumor shrinkage might allow more patients to become candidates for surgery—a potentially curative option if the cancer can be removed entirely. Other drugs targeting specific KRAS subtypes are in development, and vaccine approaches designed to prevent recurrence by training the immune system to recognize mutated KRAS are in earlier testing stages.

Dr. Andrew Coveler of the Fred Hutchinson Cancer Center, also not involved in the research, said simply: "This thing works drastically differently." For a disease that has long resisted innovation, that difference may mark a turning point. Dozens of experimental pancreatic cancer drugs are now in development, and the success of daraxonrasib suggests the undruggable may finally be within reach.