Experimental Pill Daraxonrasib Nearly Doubles Survival in Advanced Pancreatic Cancer, Study Finds
A novel pill helped patients with advanced pancreatic cancer live longer, researchers reported Sunday, marking a potential breakthrough for one of the deadliest malignancies. The drug, daraxonrasib, blocks a mutated protein that drives tumor growth in more than 90% of pancreatic cancer cases—a target that had eluded treatment for decades. The findings were published in the New England Journal of Medicine and presented Sunday at the American Society for Clinical Oncology meeting in Chicago.
Trial Design and Survival Outcomes
The study randomly assigned 500 patients with metastatic, or spreading, pancreatic cancer that had stopped responding to prior treatment to receive either daraxonrasib or additional chemotherapy. Those taking the experimental daily pills lived for a median of 13.2 months, compared with 6.7 months for chemotherapy recipients. The pill nearly doubled survival time while causing fewer severe side effects. "While not curing the cancer, it is a very large step forward," said Dr. Zev Wainberg of the University of California, Los Angeles, who helped lead the study.
Patient Response and Quality of Life
Dr. Rachna Shroff of the University of Arizona Cancer Center, who was not involved in the research, said from the American Society for Clinical Oncology meeting: "Having treated pancreatic cancer for 16 years, I actually started crying" when first seeing the study results. She noted being struck by how "patients stayed on this treatment because it was providing durable and meaningful benefit to them." The pills' effects eventually wane, but recipients used them for significantly longer than the comparison group stayed on chemotherapy, reporting less pain and a better quality of life as their tumors shrank. Many patients still were using the drug after the data was analyzed, which Wainberg said means the survival gap may widen as researchers continue tracking them.
Path to Standard Care and Expanded Access
Dr. Brian Wolpin of the Dana-Farber Cancer Institute presented the findings Sunday and said the drug should become "a new standard of care" for previously treated metastatic pancreatic cancer. He added that researchers also will explore its use earlier in the disease, including to see if tumor shrinkage might allow more patients to qualify for surgery. The most likely side effects affecting pill usage were a rash that can be severe and mouth sores, he said. Manufacturer Revolution Medicines funded the study, and the Food and Drug Administration plans to expedite review of the drug. Meanwhile, the agency is allowing "expanded access" to the experimental drug for patients who meet certain criteria. The drug garnered public attention when former U.S. Senator Ben Sasse described on "60 Minutes" how he has had less pain while taking it. Oncologists are being flooded with requests as the special access program gets started.
Pancreatic Cancer Landscape and Drug Mechanism
Pancreatic cancer is among the most deadly forms of cancer in large part because it is hard to detect before it starts spreading to other organs. The American Cancer Society estimates about 67,000 new cases will be diagnosed in the United States this year, and more than 52,000 people will die from the disease. The five-year overall survival rate is 13%. Unlike other cancers that have benefited from a variety of chemotherapy alternatives, pancreatic cancer has been harder to tackle. Cancer specialists not involved in the new research expressed optimism that this may be a turning point in the quest for new options, with dozens of experimental drugs in development. The new drug targets mutations in the RAS gene family that normally regulates cell growth. So-called KRAS mutations are especially critical in fueling pancreatic cancer, but a structure that made it hard for drugs to stick to the mutated proteins meant this cancer driver was long considered undruggable.
Context
Other recent targeted therapies for KRAS-mutated cancers include sotorasib and adagrasib, which have been approved for non-small cell lung cancer but have shown limited efficacy in pancreatic cancer.