For decades, a pancreatic cancer diagnosis has been among the most devastating words a doctor can deliver. Even with the best available treatment, most patients with advanced disease do not survive a year. Now, for the first time in more than a decade, something has changed — and the doctors who treat this cancer are struggling to contain their excitement.
A drug called daraxonrasib has doubled survival time in patients with advanced pancreatic cancer when combined with chemotherapy, according to Phase 3 clinical trial results. The Food and Drug Administration has already fast-tracked the drug for approval — and last week, it permitted the manufacturer to make daraxonrasib available to patients outside of clinical trials through an expanded access programme. Results from an earlier phase of the trial were published Wednesday in the New England Journal of Medicine, one of the most respected medical journals in the world.
“This really feels like a watershed moment,” said Dr. Brian Wolpin, who led the research and directs the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute in Boston. “It’s going to shift how we think about treatment for pancreatic cancer overall.”
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How the Drug Works — and What the Numbers Actually Mean
Pancreatic cancer is so deadly in part because of how it behaves at the molecular level. More than 90% of cases involve a mutation in the gene for a protein called RAS, which controls how cells grow. The mutation locks RAS into a permanent “on” position, allowing cancer cells to multiply without restraint. For years, researchers tried and failed to block RAS directly — leading many to consider it effectively “undruggable.”
Daraxonrasib found a way around that wall. The drug pairs with a protein called cyclophilin A inside cells, and together they act as what researchers describe as a “molecular glue” — latching onto RAS and blocking it from driving further growth. It is an elegant solution to a problem that stumped oncologists for a generation.
The Phase 1 and 2 trial results published Wednesday tracked 168 patients with advanced pancreatic cancer that had spread to the lungs and liver — all of whom had already received standard chemotherapy. In patients receiving the highest dose, the cancer stopped worsening for an average of 8.1 months. Overall survival reached approximately 15.6 months. Those numbers may sound modest in isolation. In the context of a disease where many patients do not survive a year after diagnosis and just 3% of metastatic cases are alive five years later, they represent a seismic shift.
The Phase 3 results go further. Patients receiving chemotherapy alone survived an average of 6.7 months. Those receiving daraxonrasib alongside chemotherapy survived an average of 13.2 months — nearly double. The Phase 3 trial also included patients without the KRAS mutation, suggesting the drug may offer benefits across a broader range of pancreatic cancer cases than initially anticipated.
Side effects are real and in some cases severe. The most notable is a blistering rash described by one clinical trial participant as “nuclear.” Mouth and throat sores, vomiting, and diarrhoea were also reported. Around 30% of patients experienced severe side effects, and eight left the trial because of them. Wolpin noted that some patients needed temporary breaks from the drug to allow the rash to settle — but emphasised that most found the drug significantly more tolerable than chemotherapy. “Most patients greatly prefer the ability to take a pill every day rather than do all of those infusions,” he said.
The enthusiasm among oncologists not involved in the trial has been striking. “Those of us who take care of this disease are frankly a little cynical about new data,” said one gastrointestinal oncologist at a major cancer centre. “Most of the time it is overhyped. But this is a big deal. This drug is the most exciting thing in pancreas cancer in over a decade.” Another surgical oncologist at Vanderbilt University Medical Center called the results “groundbreaking” — a word, he said, he does not use lightly.
More than 67,000 people in the United States are expected to receive a pancreatic cancer diagnosis this year. Over 52,000 are predicted to die of the disease. There is no screening programme, and 80% of patients are diagnosed at later stages when treatment options are limited. Daraxonrasib will not solve all of that — but it may, for the first time in a very long time, give patients and their doctors something to hold on to.
Researchers are also studying whether the drug works in RAS-mutated colorectal and lung cancers, and two smaller studies presented in April found survival benefits when daraxonrasib was used as a first-line therapy rather than after chemotherapy had already been tried. Full Phase 3 results are scheduled to be presented later this month at the American Society of Clinical Oncology’s annual meeting.
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