May 31, 2026 is a date that the scientific community will surely remember as potentially revolutionary: a clinical trial has finally found a potential new avenue of treatment. But is it really the revolution, the cure we were all waiting for?
Pancreatic cancer
Metastatic pancreatic cancer is still considered incurable, with a low probability of survival a few years, if not months, after diagnosis, and the only treatment available, which is not very effective, is chemotherapy.
The pathology represents approximately 3% of cancer diagnoses in the United States, where this innovative trial was conducted: theAmerican Cancer Society estimates that in 2026, 35,160 men and 32,340 women will be diagnosed with this tumor, and that approximately 95% of cases will be pancreatic ductal adenocarcinoma (PDAC).
More than half of pancreatic cancer cases are diagnosed after the onset of metastases, and the 5-year relative survival rate is approximately 3%. Chemotherapy is generally administered as first-line treatment and, if necessary, as second-line treatment, but with second-line chemotherapy the median progression-free survival (PFS) is 3-4 months and the median overall survival is 6-7 months.
We also know that more than 90% of metastatic PDACs are caused by a mutation in the KRAS gene, called the RAS G12 variant, which results in a hyperactive KRAS protein.
What the new study showed
The RAS protein, considered the “engine” of the growth of this tumor, has always been considered “unassailable” (or almost): the (few) previously available drugs that deactivate this protein, called RAS inhibitors, are in fact specific only for one of the altered variants of the protein.
Few therapies are available for patients with previously treated metastatic pancreatic cancer, and these therapies have modest efficacy and considerable toxicity – explains Brian Wolpin, who led the research – The RASolute 302 study was designed to evaluate a multiselective RAS(ON) inhibitor as a second-line treatment for patients with metastatic pancreatic cancer, with the goal of defining a new standard of care for these patients that is more effective and has fewer side effects than currently available chemotherapies
This latest trial has now demonstrated, in particular, that the administration of daraxonrasib, a multiselective inhibitor of the RAS protein, can improve progression-free survival and overall survival in patients affected by metastatic pancreatic ductal adenocarcinoma (mPDAC), regardless of the presence or absence of a RAS mutation in the tumor.
How the study was conducted and the conclusions
The research was conducted on a population of 500 patients from North America, Europe and Asia (half women and half men, with a median age of 66 years and still able to carry out most of their daily activities), suffering from previously treated metastatic pancreatic cancer, by administering half of them the daraxonrasib and the other half standard chemotherapy.
Result? The RAS(ON) multi-selective daraxonrasib may improve progression-free survival and overall survival in patients with mPDAC, regardless of whether or not the tumor has a RAS mutation.
In particular, the results of this first phase 3 study on a multiselective RAS(ON) inhibitor, conducted after demonstrating good results in terms of tolerance and safety, demonstrate the efficacy of daraxonrasib in the treatment of RAS-mutant and RAS-mutated metastatic pancreatic ductal adenocarcinoma (mPDAC) wild type: in treated patients, daraxonrasib almost doubled survival with fewer side effects compared to chemotherapy.
What changes for patients and their chances of recovery
Unfortunately – we have said it several times – the therapy is able to improve patient survival, but not to eradicate the disease, which remains incurable. However, one year after starting therapy, 53% of patients treated with the drug were alive daraxonrasib versus 17% of those who received chemotherapy. And this result had never been achieved before.
Said in “colloquial” terms, a wall has finally been knocked down, that of the RAS protein, which from today is a target that can be attacked and potentially destroyed. What has been achieved is truly a revolution scientifically speaking, because it can completely change the approach to therapies against this unforgiving disease.
The road to a world free from pancreatic cancer, however, is still very long.
The study was presented at the annual conference ofAmerican Society of Clinical Oncology (ASCO) and funded by Revolution Medicines.
