A novel pill helped people with advanced pancreatic cancer live longer, researchers reported Sunday, raising hopes of long-needed better treatments for one of the deadliest types of cancer. “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.
The drug is called daraxonrasib, and it blocks a mutated protein that fuels tumour growth in more than 90% of pancreatic cancer cases — a target that had eluded treatment for decades.
Study Results Show Significant Survival Improvement
The daily pills nearly doubled survival time, with fewer severe side effects, in a study that randomly assigned the experimental drug or more chemotherapy to 500 patients whose metastatic, or spreading, cancer had quit responding to prior treatment. The findings were published in the New England Journal of Medicine and presented Sunday at the American Society for Clinical Oncology meeting in Chicago.
Those taking daraxonrasib lived for a median of 13.2 months compared with 6.7 months for chemotherapy recipients. While that may seem like a small improvement, Wainberg said it marked the first drug to show a substantial advantage over chemotherapy.
“Having treated pancreatic cancer for 16 years, I actually started crying" when first seeing the study results, Dr. Rachna Shroff of the University of Arizona Cancer Center, who wasn't involved with the research, said from the ASCO meeting. She was 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 tumours shrank. Many still were using the drug after the data was analyzed, which Wainberg said means the survival gap may widen as researchers continue tracking them.
Potential to Become a New Standard of Care
Dr. Brian Wolpin, of the Dana-Farber Cancer Institute, presented the findings on Sunday. He said the drug should become “a new standard of care” for previously treated metastatic pancreatic cancer, adding that researchers also will explore its use earlier in the disease, including to see if tumour shrinkage might let more patients qualify for surgery.
Side effects most likely to affect pill usage were a rash that can be severe and mouth sores, he said.
Maker Revolution Medicines funded the study, and the Food and Drug Administration plans to expedite review of the drug. Meanwhile, the agency is allowing what’s called “expanded access” to the experimental drug for patients who meet certain criteria. The drug garnered public attention when former U.S. Sen. Ben Sasse described on “60 Minutes” how he's had less pain while taking it. Oncologists are being flooded with requests as the special access program gets started.
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Why Pancreatic Cancer Is So Difficult to Treat
Pancreatic cancer is among the most deadly forms in large part because it’s 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 U.S. this year and more than 52,000 people will die from the disease. The five-year overall survival rate is 13%.
Unlike with other cancers that have benefitted 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.
How the Drug Works and What’s Next
The new drug targets mutations in the RAS gene family that normally regulate 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.”
Revolution Medicines’ drug uses what’s essentially a molecular glue to bind with multiple KRAS subtypes. Wainberg said researchers will next probe whether the drug worked better in certain of those subtypes.
The drug will change pancreatic cancer treatment, said Dr. Andrew Coveler of the Fred Hutchinson Cancer Center, who wasn’t involved in the research.
“This thing works drastically differently,” he said.
Wainberg said other drugs in development target specific KRAS subtypes. Other 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.
- with files from The Associated Press
