Metastatic pancreatic cancer: experimental drug doubles survival
For advanced adenocarcinoma, treatment options have limited efficacy and patients have a poor prognosis: a new phase could open up
The oral investigational drug daraxonsasib, a multisense inhibitor of the RAS oncogene, proved to be a game changer in metastatic pancreatic cancer, leading to a doubling of survival compared to patients treated with conventional chemotherapy. The 248 patients treated with daraxonsasib showed a doubling of median survival (13.2 months, compared to 6.7 months) compared to 252 patients treated with chemotherapy. Never before had any drug reached this milestone. This is why the results of the international phase 3 study RASolute 302, presented before a worldwide audience of oncologists at the ASCO congress in Chicago and published simultaneously in the New England Journal of Medicine, were greeted by a standing ovation. Enthusiasm galore, but also a liberating applause because for advanced pancreatic adenocarcinoma the available treatment options have limited efficacy and these patients continue to have a poor prognosis. Daraxonrasib does not promise a cure for pancreatic cancer, which remains one of the most difficult to treat; but it does represent a major step forward. The drug is currently spearheaded by Revolution Medicines, a pharma company with a pipeline specialising in the development of innovative targeted therapies for RAS mutation-dependent cancers.
The story of the results at the Asco congress
When the study coordinator, Brian M. Wolpin, director of the Hale Family Center for Pancreatic Cancer Research and Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute (Boston), projected the slide showing the 60% mortality reduction produced by daraxorasib, the oncologists attending the plenary session of the ASCO 2026 congress burst into endless applause (lasting 42 seconds), accompanied by cheers, whistles and all kinds of appreciation. A stadium cheer for life, for those months snatched from death, a 'grand slam' (in the definition of Julie Gralow, vice-president of ASCO), for patients and researchers alike.
But there is more. Here, months gained from death are also months lived better, without the pain that accompanies the end of this cancer and at the price of more than tolerable treatment side effects (skin rash and stomatitis being the most frequent).
How the new drug works
A smart drug, daraxonrasib works 'cleanly', silencing the RAS oncogene that, when activated, induces uncontrolled tumour growth (over 90% of pancreatic tumours harbour an oncogenic RAS mutation). The RAS oncogene in the 'on' position is like a switch that always stays on. Daraxonrasib succeeds in switching it off and so far no other therapy has been able to do this in adenocarcinoma of the pancreas. For decades the RAS was considered a 'non-pharmacological' (undruggable) target. Then came daraxonrasib, a RAS inhibitor, or rather of the RAS(ON), i.e. it binds to the blocked 'on' form of the deadly switch. It is an oral drug (you take one 300mg tablet a day). The US FDA has granted it breakthrough therapy designation for the treatment of pancreatic cancer with KRAS G12X mutations. And that is hardly surprising.
A new standard of care
'Daraxonrasib represents a new standard of care in the second-line treatment of adenocarcinoma of the pancreas,' commented the discussant of the presentation, Dr Jennifer J. Knox, Princess Margaret Cancer Centre and University of Toronto (Canada). The other point I want to emphasise is that RAS-targeted therapy should play a predominant role in clinical trials, across the full spectrum of clinical manifestations of pancreatic cancer, either as monotherapy or in combination, to benefit more patients and improve survival and quality of life."
