Study finds daraxonrasib extends survival in previously treated metastatic pancreatic cancer
Dr. Brian Wolpin of the Dana-Farber Cancer Institute presented the findings Sunday at the American Society for Clinical Oncology meeting in Chicago. The study randomly assigned patients to receive either daraxonrasib, a daily pill made by Revolution Medicines, or standard chemotherapy. All 500 participants had metastatic cancer that had progressed after earlier treatment.
The drug targets mutations in the KRAS gene family, which normally regulates cell growth. So-called KRAS mutations are especially common in pancreatic cancer, appearing in more than 90% of cases. A structural feature of the mutated proteins had made it difficult for drugs to bind to them, and KRAS was long considered “undruggable.” Daraxonrasib uses what researchers described as a molecular glue to attach to multiple KRAS subtypes.
“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.
Wainberg noted that the drug was the first to show a substantial survival advantage over chemotherapy in this patient population. He said many participants were still taking the drug when the data was analyzed, which means the survival gap between the two groups may widen as researchers continue tracking them.
Dr. Rachna Shroff of the University of Arizona Cancer Center, who was not involved in the research, said from the ASCO meeting that she was moved by the results. “Having treated pancreatic cancer for 16 years, I actually started crying” when first seeing the data, Shroff said. She added that patients stayed on the treatment because it was “providing durable and meaningful benefit to them.”
Recipients of the drug reported less pain and a better quality of life as their tumors shrank, and they used the medication significantly longer than the comparison group stayed on chemotherapy. The pills’ effects eventually wane.
Side effects most likely to affect continued use of the drug were a rash that can be severe and mouth sores, Wolpin said.
Dr. Andrew Coveler of the Fred Hutchinson Cancer Center, who was not involved in the research, said the drug would change pancreatic cancer treatment. “This thing works drastically differently,” Coveler said.
Wolpin said the drug should become a new standard of care for previously treated metastatic pancreatic cancer. He added that researchers plan to explore using it earlier in the course of the disease, including whether tumor shrinkage might allow more patients to qualify for surgery.
Pancreatic cancer is among the deadliest forms of the disease largely because it is hard to detect before it spreads 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 it. The five-year overall survival rate is 13%. Unlike other cancers that have benefited from a range of chemotherapy alternatives, pancreatic cancer has proven harder to treat.
Revolution Medicines funded the study. The FDA plans to expedite review of the drug and has begun an expanded access program for patients who meet certain criteria. The program drew public attention when former U.S. Sen. Ben Sasse described on “60 Minutes” how he experienced less pain while taking the drug. Oncologists said they have been flooded with requests as the access program gets started.
Other drugs in development target specific KRAS subtypes, Wainberg said. Additional approaches in earlier stages of testing include vaccines designed to prevent recurrence after pancreatic cancer surgery by teaching the immune system to recognize the mutated protein.