New treatments that target the KRAS gene mutation are offering significant hope for patients with advanced pancreatic cancer, with clinical trial results showing that the drug daraxonrasib can effectively double survival time compared with standard chemotherapy.
The findings, from a phase 3 trial involving 500 patients whose cancer had spread to other organs, represent what experts are calling a “landscape-changing” advance in a disease that has seen little improvement in survival outcomes over the past half-century. Patients who received daraxonrasib had a median overall survival of 13.2 months, compared with 6.6 months for those given chemotherapy — effectively doubling the time they lived.
Targeting the KRAS Mutation
At the heart of this breakthrough is the KRAS gene mutation, a genetic driver found in more than 90% of pancreatic tumours. For decades, KRAS was considered “undruggable” because its smooth surface made it exceptionally difficult for drugs to bind to it and block its activity. The mutation acts like a stuck accelerator, sending constant signals for cancer cells to grow and divide uncontrollably, enabling tumours to spread and resist conventional treatments.
Daraxonrasib is a targeted therapy designed to inhibit the KRAS mutation directly. Classified as a “pan-RAS inhibitor,” it can tackle several forms of the mutation — including G12D, G12V, G12R and Q61X — which is particularly significant because the G12D variant is the most common in pancreatic cancer. Administered as a once-daily oral pill, the drug works by blocking the signals that drive uncontrolled cell growth, thereby preventing tumours from spreading and, in many cases, shrinking existing tumours.
The ability to target such a fundamental driver of pancreatic cancer marks a conceptual shift. Until now, the only treatment options for advanced disease have been chemotherapy and, where possible, surgery — but the vast majority of patients are diagnosed too late for surgery to be curative. The disease is notorious for its late presentation: half of all people with pancreatic cancer die within just three months of diagnosis.
In the trial, patients who had already received prior treatment and were still able to perform most daily activities were given either daraxonrasib or standard chemotherapy. While the median time without the disease progressing was similar in both arms — 7.3 months for daraxonrasib and 7.2 months for chemotherapy — the overall survival benefit was substantial and regarded as clinically meaningful.
Importantly, the drug also demonstrated a more favourable side-effect profile. Severe side effects occurred in 43.6% of patients on daraxonrasib, compared with 57.5% on chemotherapy. Moreover, only 1.2% of patients stopped treatment because of side effects, versus 11.2% in the chemotherapy group. This improved tolerability is considered a major advantage, allowing patients to maintain quality of life while receiving treatment.
The UK context underscores the urgency of such advances. Around 11,500 new cases of pancreatic cancer are diagnosed each year in the UK, and approximately 10,200 people die from the disease annually. It is the fifth most common cause of cancer death, accounting for 6% of all cancer fatalities. Survival rates remain desperately low: overall, only about 5% of patients survive for five years or more. In England, one-year survival stands at roughly 27.7%, and five-year survival at around 8.3%. Over the past 50 years, five-year survival has crept up from 2.4% in the 1970s to just 4.3% by 2018 — a rate of improvement that charities describe as tragically slow.
Charity Calls for Fast-Track Approval
Reacting to the findings, Anna Jewell, director of services, research and innovation at Pancreatic Cancer UK, said: “These new treatments targeting KRAS mutations are some of the most exciting developments we have seen in pancreatic cancer for a very long time.” She emphasised that by blocking KRAS activity, daraxonrasib has shown improved survival, giving patients “months more precious time with their loved ones.”
Other experts have echoed that assessment. Rachna Shroff, chief of the division of haematology/oncology at the University of Arizona Cancer Centre, stated: “These results are landscape-changing for metastatic pancreatic cancer patients with a KRAS mutation. We are seeing unprecedented survival and efficacy in second-line treatment with an expected safety profile. The RAS revolution is here, and this study is proof of principle that targeting KRAS in pancreatic cancer is feasible and effective.”
Paula Hanford, chief executive of UK-based Pancreatic Cancer Action, described the discovery as “one of the most significant developments in treatment that she had ever seen,” highlighting the limited options and devastatingly low survival rates facing patients.
Pancreatic Cancer UK is now calling for clinical trials for daraxonrasib and similar KRAS inhibitor drugs to be made available in the UK, and for these new treatments to be fast-tracked for approval. The charity argues that without swift action, British patients could miss out on a therapy that offers the first real improvement in survival for advanced pancreatic cancer in decades. Research is also ongoing into combining daraxonrasib with other treatments, potentially reducing the risk of drug resistance, and the success in targeting KRAS may pave the way for breakthroughs in other cancers driven by RAS genes.