A pill called daraxonrasib has been shown to increase survival rates in previously treated people with metastatic pancreatic cancer, according to a study published in the New England Journal of Medicine. While the drug has yet to be approved by the FDA, people with pancreatic cancer who have had chemotherapy can access daraxonrasib at Duke Health through an expanded access program. “We haven't had advances in metastatic pancreatic cancer like this for more than 15 years.” said Duke Health medical oncologist Niharika B. Mettu, MD, PhD.
The Challenges of Treating Pancreatic Cancer
Pancreatic cancer has historically been hard to treat, according to Dr. Mettu. It lacks early screening tests and has often spread by the time it is discovered. Only two chemotherapy regimens are in the standard treatment toolbox, and they often have challenging side effects. The fibrous nature of pancreatic tumors means that chemotherapy doesn't penetrate them well. Finally, there aren't a lot of immune cells in pancreatic cancers, so it's harder to take advantage of the body's immune system to fight the disease.
Promising Results in the Fight Against Pancreatic Cancer
In May, The New England Journal of Medicine published a study that compared outcomes from daraxonrasib with a standard chemotherapy regimen in 500 patients who had already received treatment for metastatic pancreatic cancer. The patients who received daraxonrasib lived over twice as long, with fewer side effects.
Dr. Mettu noted that Duke participated in the trial that led to the drug’s availability and continues to be involved in studies that are looking at other ways of using daraxonrasib to treat pancreatic cancer.
How Daraxonrasib Works
Daraxonrasib is considered a targeted therapy because it responds to a gene mutation, said Dr. Mettu. The KRAS gene produces a protein that should work like an on/off switch. Mutations keep the protein stuck in the "on" position, continuously telling cells to grow and divide uncontrollably. Daraxonrasib binds first with a protein called CypA and then to the KRAS protein, forming a barrier that prevents the grow-and-divide signals from reaching their targets.
"The vast majority of -- if not all -- people with pancreatic cancer have a chance of benefiting from the drug," said Dr. Mettu. That's because 90% of pancreatic cancers show a KRAS mutation, and unlike previous KRAS-based therapies, daraxonrasib responds to any variant of the mutation. Interestingly, daraxonrasib seems to work even when a KRAS mutation isn't present. "Researchers are trying to understand why," Dr. Mettu said.
Daraxonrasib's side effects, including rashes and diarrhea, need to be closely monitored and cared for by an experienced team, said Dr. Mettu. "Because Duke is experienced with daraxonrasib, we are well-equipped to help our patients navigate side effects. We work closely with Duke dermatology, gastroenterology, and palliative care teams to help relieve symptoms."
The Future of Daraxonrasib
Because KRAS mutations are found in several other cancers, such as colon and non-small-cell lung cancer, daraxonrasib may be beneficial in treating those diseases, too. "The future is brighter for those battling this hard disease, and we are on the brink of even more exciting data to come," said Dr. Mettu.
