Hope for people with pancreatic cancer: A new drug doubles the survival time of patients with metastatic pancreatic cancer and slows down the progression of the deadly tumor disease better than standard chemotherapy, as a clinical study demonstrates. The active ingredient daraxonrasib inhibits cancer-promoting gene mutations that occur in 90 percent of pancreatic cancer cases. Oncologists speak of a revolutionary breakthrough and a paradigm shift in this difficult-to-treat type of cancer.
Pancreatic cancer is one of the most aggressive and difficult types of cancer to fight: few people affected survive longer than a year after diagnosis; the survival rate after five years is only seven percent. Even a combination of several chemotherapy drugs can rarely stop the progression of the often inoperable tumors. In addition, pancreatic cancer initially causes hardly any specific symptoms, so the cancer is often only recognized when it has already formed metastases.
Inhibitor against mutated RAS oncogenes
But now there is a potentially decisive advance: A research team led by Eileen O’Reilly from the Memorial Sloan Kettering Cancer Center in New York has developed and tested an active ingredient that targets a main driver of aggressive pancreatic cancer, a so-called RAS oncogene. This gene is mutated in 90 percent of pancreatic cancer patients and is therefore overactive. The result is excessive growth and degeneration of the cells.
The newly developed active ingredient daraxonrasib inhibits the signaling pathways of the mutated RAS oncogene. It is not given as an infusion, but taken daily as a tablet. O’Reilly and her team have now tested how well this drug works compared to standard chemotherapy in a phase 3 clinical study with 500 patients. All participants suffered from metastatic pancreatic cancer and had already undergone their first chemotherapy. Half of them now received daraxonrasib, the other a second chemotherapy drug, as was usual before.
Doubled survival time, fewer serious side effects
The result was clear: the cancer patients who received daraxonrasib survived around twice as long as those who received standard chemotherapy – 13.2 months instead of just 6.7 months. The further growth of pancreatic cancer and metastases was also significantly slowed down, as the researchers report: In around 32 percent of the cancer patients treated with daraxonrasib, the tumors shrank or even disappeared; with chemotherapy, this only happened in a good eleven percent.
Also positive: Daraxonrasib also causes side effects such as diarrhea, nausea, skin rashes and inflammation of the mucous membranes. However, these were less serious than with standard chemotherapy. “Side effects that led to therapy being discontinued only occurred in 1.2 percent of patients, compared to 11.2 percent in the chemotherapy group,” report O’Reilly and her team. Overall, patients treated with daraxonrasib reported improved quality of life.
“Paradigm shift for pancreatic cancer”
“This study represents a paradigm shift for pancreatic cancer,” comments oncologist Dieter Saur, Professor of Translational Tumor Research at the Technical University of Munich (TUM) and the German Cancer Research Center Heidelberg, who was not involved in the study. “For the first time, we see in a large randomized phase III study that direct pharmacological inhibition of RAS in previously treated metastatic pancreatic cancer brings a very clear survival advantage compared to chemotherapy.”
The research team also sees things similarly positively: “For many years we have been looking for a method to block mutated RAS oncogenes in pancreatic cancer,” says senior author Brian Wolpin from the Dana-Farber Cancer Institute in Boston. “This is the first drug that broadly inhibits RAS and has the potential to help many patients with pancreatic cancer.”
Approval could come soon
Because more than 90 percent of pancreatic cancer patients carry mutations in a RAS oncogene, the new inhibitor could bring clear survival benefits to the majority of those affected, say the researchers. “It is a therapy that could be relevant for almost all patients with metastatic pancreatic cancer,” says Wolpin. “If this drug is approved by the FDA, it could lead to a dramatic change in the treatment of pancreatic cancer.”
According to experts, daraxonrasib could be approved relatively quickly. In the USA, the drug authority has already given the active ingredient breakthrough therapy and orphan drug status based on the convincing study results. In addition, the FDA has already approved daraxonrasib to be administered to selected patients in a controlled and monitored setting prior to formal approval. “This is not yet a regular approval – but it shows that the authority recognizes the high medical need and the importance of the data,” says Saur.
According to the oncologist, the active ingredient daraxonrasib could soon also benefit cancer patients in Europe. “If the data are confirmed by the regulatory authorities, I expect that daraxonrasib will very quickly become a new standard option in second-line therapy for metastatic pancreatic cancer – especially in patients with RAS-G12 mutated tumors,” explains Saur.
Hope for other types of cancer too
Mutations in the RAS oncogene not only occur in pancreatic cancer, but are also considered to be drivers in other types of cancer. Around half of colon tumors show such RAS mutations; this mutation also occurs in non-small cell lung cancer and other solid tumors. The first clinical studies on the effect of daraxonrasib against non-small cell lung cancer are already underway.
“Given its ability to inhibit mutated and unmutated proteins of the RAS oncogenes, daraxonrasib has broad applicability that has not existed before,” says Wolpin.
Source: Eileen O’Reilly (Memorial Sloan Kettering Cancer Center, New York) et al., New England Journal of Medicine, 2026; doi: 10.1056/NEJMoa2605555