Pancreatic cancer pill extends survival across RAS types at ESMO

A daily pill that roughly doubled survival in previously treated pancreatic cancer appears to help across every RAS subtype tested, including people whose tumours showed no RAS mutation at all. That's the headline from new subgroup data on daraxonrasib (Rasonque), presented at the European Society for Medical Oncology (ESMO) Congress in Madrid on 23 October 2026.

The drug was already approved in the US two months earlier. The ESMO analysis matters because it speaks to a practical question doctors face every week: does the tumour's genetic profile change who should get it?

What RASolute 302 tested

RASolute 302 (NCT06625320) was a global phase 3 trial in 500 adults with metastatic pancreatic adenocarcinoma whose cancer had grown after earlier treatment. It was open-label, meaning patients and doctors knew which treatment was given.

Patients were randomly assigned to one of two options:

• daraxonrasib 300 mg taken by mouth once a day (248 patients)
• the investigator's choice of one of four standard chemotherapy regimens (252 patients)

The headline results, first presented at the 2026 American Society of Clinical Oncology meeting and published in the New England Journal of Medicine, were striking for this disease.

The overall survival hazard ratio was 0.40 (95% CI 0.30 to 0.53). Put simply, the risk of death at any point in the trial was 60% lower on daraxonrasib.

Those figures led the FDA to approve the drug on 26 August 2026, months ahead of its target date. Angelo de Claro of the FDA's oncology review team said: "This drug showed unprecedented results in an area of high unmet need."

Why RAS matters in pancreatic cancer

RAS proteins act as on and off switches for cell growth. In most pancreatic cancers, a mutation in the KRAS gene jams the switch on. For decades RAS was considered almost impossible to drug.

Daraxonrasib is what Revolution Medicines calls a RAS(ON) multi-selective inhibitor. It is designed to block the active, switched-on form of several RAS variants at once. Earlier RAS drugs, such as those for lung cancer, target a single mutation called G12C, which is rare in pancreatic tumours.

The trial included patients with G12D, G12V and G12R mutations, the most common in pancreatic cancer. It also enrolled people with G13 or Q61 mutations and people with no identified RAS mutation.

What the ESMO subgroup analysis showed

Zev Wainberg of UCLA presented the analysis as late-breaking abstract LBA82. It used the same data cut-off as the main results, 10 February 2026, with a median follow-up of 8.5 months. According to Revolution Medicines, overall survival favoured daraxonrasib in every subgroup examined.

By RAS mutation type:

By the chemotherapy it was compared against:

• gemcitabine plus nab-paclitaxel, hazard ratio 0.45 (0.32 to 0.65)
• modified FOLFIRINOX or FOLFOX, 0.46 (0.23 to 0.95)
• nanoliposomal irinotecan with fluorouracil and leucovorin, 0.32 (0.18 to 0.58)

By earlier treatment, the hazard ratio was 0.36 (0.17 to 0.75) in people whose cancer came back within six months of surgery-related chemotherapy. In those who'd had one previous line of treatment for spread disease it was 0.43 (0.32 to 0.58).

How to read those subgroup numbers

Every hazard ratio sits below 1, which points the same way as the main result. That consistency is reassuring.

But look at the confidence intervals. For G12R, Q61 and the no-mutation group, the ranges cross 1. For the no-mutation group the range runs from 0.09 to 1.98. That means the data are compatible with a large benefit, no benefit, or in theory some harm. These groups were small, and the analyses were exploratory, so they weren't designed to prove an effect in each subgroup on its own.

Wainberg's interpretation was upbeat. "The overall survival benefit was seen consistently across all evaluated tumor RAS profiles," he said in the company release. He added that this pointed to the drug's potential to help the broad population of patients with the disease.

A cautious reader would say the G12D and G12V results are solid, and the rest are encouraging but uncertain. Our guide on how to read clinical trial results explains confidence intervals in more detail.

The practical point is the FDA label. It doesn't require a RAS test. The drug is approved for adults with metastatic pancreatic adenocarcinoma who have had at least one prior systemic therapy, or who can't have multi-drug treatment. The ESMO data broadly support that broad label.

Living with the treatment day to day

Daraxonrasib is a tablet taken once a day at home. For many people with advanced cancer, that alone is a change. Second-line chemotherapy usually means regular trips to a day unit for infusions, and some regimens involve a pump worn at home for a couple of days.

A pill doesn't remove the need for close follow-up. The label asks doctors to watch for skin, mouth and gut problems and for new breathing symptoms, and to adjust or pause the dose when they appear. It also lists drug interactions, so anyone starting it should make sure their oncology team knows about every other medicine and supplement they take.

Side effects

Daraxonrasib isn't gentle, though its problems differ from chemotherapy's. From the US prescribing information:

• skin problems, mostly rash, in 86% of patients, severe in 10%
• mouth sores (stomatitis) in 57%, severe in 9%
• diarrhoea in 63%, severe in 6%
• bowel perforation in 0.9%, with one death
• lung inflammation (interstitial lung disease or pneumonitis) in 2.4%, with one death

Serious side effects occurred in 30% of patients. Only 2.9% stopped the drug permanently because of side effects.

The label recommends starting skin protection before the first dose. That means a steroid cream on the face and chest, moisturisers, sun protection of SPF 30 or more, and considering an antibiotic such as doxycycline.

Putting the survival gain in context

Pancreatic cancer is one of the hardest cancers to treat. The FDA puts the number of new US cases at about 67,000 a year, and 90 to 95% of them are adenocarcinomas, the type daraxonrasib is approved for. Revolution Medicines cites estimates that about 80% of patients are diagnosed after the cancer has spread, and that five-year survival with metastatic disease is around 3% worldwide.

In that setting, a rise in median survival from 6.7 to 13.2 months is a big shift for patients, families and the specialists who have had very little to offer at this stage. Picture 100 people starting second-line treatment after their first chemotherapy has stopped working. On chemotherapy, half would have died by about 6.7 months. On daraxonrasib, half would still be alive at 13.2 months, nearly twice as long. Follow-up is still short and this is no cure. Even so, it adds roughly six months for a typical patient, delivered as a pill.

Open-label design is worth remembering. It matters less for survival, which is an objective outcome, than for things like quality of life scores. Our explainer on open-label vs blinded trials goes into this.

Where the drug is available

In the US, daraxonrasib is approved and on the market. The FDA review used several fast-track tools, including breakthrough therapy and priority review, and ran under Project Orbis with Health Canada.

In Europe, the European Medicines Agency's Committee for Medicinal Products for Human Use has given a positive opinion. A final decision from the European Commission is pending. Outside the US, the company says the drug remains investigational until regulators approve it. In the UK, use on the NHS would also need MHRA approval and a NICE appraisal, which our guide to how new medicines get approved explains.

Revolution Medicines is also testing the drug earlier in pancreatic cancer and in RAS-mutant lung cancer. For another example of a targeted drug changing a hard-to-treat gut cancer, see our report on zanidatamab's three-year survival data.

Questions to ask your oncologist

If you or a family member has pancreatic cancer that has grown after first treatment:

1. Is daraxonrasib an option here, or is a trial or access scheme available?
2. Has my tumour had RAS testing, and does the result change anything?
3. What skin and mouth care should I start before the first dose?
4. How would we spot bowel or lung side effects early?

This article reports trial results and regulatory news for general information. It is not medical advice. Please discuss any treatment with your own doctor.