Most patients with advanced pancreatic cancer treated with daraxonrasib will see the drug lose its effect, and researchers are starting to identify why, according to a Sept. 30 report in The New York Times.
The FDA approved Revolution Medicines’ daraxonrasib Aug. 26 after trial data showed pancreatic cancer patients who received the drug lived almost twice as long as those on chemotherapy. It is the first targeted drug approved for pancreatic cancer that acts on multiple forms of RAS, a protein that drives tumor growth in most pancreatic adenocarcinoma cases.
Former Nebraska Sen. Ben Sasse joined a daraxonrasib trial at Houston-based University of Texas MD Anderson Cancer Center weeks after his stage 4 pancreatic cancer diagnosis in December 2025. In April, he told the Times that his tumor volume had shrunk 76%, but by September he said his cancer had become resistant to the drug.
Here are five things to know:
- Treatment response can fade after roughly seven months, even in patients who initially benefit, according to the Times. Andrew Aguirre, MD, PhD, a pancreatic cancer specialist at Boston-based Dana-Farber Cancer Institute, told the Times that resistance develops in nearly every patient on the drug.
- A study published Aug. 11 in Nature Medicine analyzed blood samples from 44 patients in the drug’s phase 1/2 trial, taken before treatment and after their cancer progressed.
Resistance-linked genetic changes were found in 59% of patients. The most common was extra copies of the mutant KRAS gene, found in 36% of patients. Patients whose tumors carried a TP53 mutation before treatment were more likely to develop the extra KRAS copies. - No genetic driver was identified in roughly 40% of patients, suggesting their tumors resisted the drug through other means. Dr. Aguirre told the Times that changes not driven by mutations, either within tumors or in their surrounding tissue, may play a role.
- A separate study is tracking how tumors change on the drug. Dr. Aguirre presented the study’s preliminary findings Sept. 25 at the American Association for Cancer Research’s pancreatic cancer conference in San Diego.
For the study, researchers enrolled 66 patients to have tumors biopsied at three points: before treatment, about two weeks into treatment and at progression.
Two weeks into treatment, about half the cancer cells were gone. Many of the remaining cells resembled cells that respond to chemotherapy, Revolution Medicines CEO Mark Goldsmith, MD, PhD, told the Times. - Some cancer centers began preparing for daraxonrasib resistance before FDA approval. Mitesh Borad, MD, leader of Mayo Clinic Comprehensive Cancer Center in Phoenix’s Novel Therapeutics and Therapeutic Modalities Program, told Becker’s the center was planning trials of drugs aimed at tumors that no longer respond to daraxonrasib.
