A new experimental drug has offered a rare ray of hope in the fight against pancreatic cancer, one of the deadliest and most difficult-to-treat malignancies.
Researchers have reported that a daily oral pill, called daraxonrasib, nearly doubled survival time in patients with advanced pancreatic cancer whose disease had stopped responding to previous treatments.
The findings, presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago and simultaneously published in the New England Journal of Medicine, are being hailed by cancer experts as a potentially transformative moment for pancreatic cancer treatment.
"Pancreatic cancer is one of the most difficult cancers to treat. For patients whose disease has already spread and stops responding to the first treatment, the outlook is usually poor. Current second-line treatments generally help patients live for only about 5–6 months on average, highlighting a major unmet medical need," says Dr Deepak Sundriyal, AIIMS, Rishikesh. "Any therapy that significantly extends survival while maintaining quality of life is an important development."
Dr Anant Ramaswamy, professor, Dept. of Medical Oncology, Tata Memorial Centre, Mumbai, who specialises in gastrointestinal cancers and geriatric oncology, agrees with Dr Sundriyal. "Pancreatic cancers are considered amongst the most difficult to treat malignancies and there has been a fair degree of nihilism in the oncology community when it comes to treating this group of cancers. Unlike a lot of other cancers, such as breast cancers and lung cancers, where treatment options have extended life-spans to 5 years and beyond, progress in pancreatic cancers has been at a snail’s pace. Survival rates in the late 90s were around 6 months; three decades later, survivals barely reach 12 months with aggressive multi-drug chemotherapy. In such a scenario, when an oral tablet almost doubles survival, that too in patients who have already received chemotherapy, there is reason to look for a silver lining."
Also, doctors agree that Pancreatic cancer is notorious for being diagnosed late, often after it has already spread to other organs. Symptoms are usually vague in the early stages, making timely detection difficult, which is also why survival rates remain very low.
According to the American Cancer Society, around 67,000 people are expected to be diagnosed with pancreatic cancer in the United States this year, while more than 52,000 are projected to die from the disease. The five-year survival rate stands at just 13 per cent.
For patients whose cancer progresses despite chemotherapy, treatment options are particularly limited and that is where daraxonrasib could potentially change the landscape.
The drug works by targeting mutations in the KRAS gene, which are found in more than 90 per cent of pancreatic cancers.
KRAS mutations drive uncontrolled tumour growth, but for decades, scientists struggled to develop drugs capable of effectively targeting the protein. The challenge was so formidable that KRAS was often described as "undruggable" within the oncology community.
Dr Amol Akhade, consultant, medical oncology at Fortis Hospital Mulund, explains how the study also reinforces a broader scientific achievement, "that of KRAS, once considered 'undruggable', it can now be successfully targeted, thereby marking the beginning of a more personalised treatment approach for patients with KRAS-mutated pancreatic cancer".
Daraxonrasib belongs to a new generation of targeted therapies designed to overcome that hurdle. The drug uses what researchers describe as a molecular binding mechanism that allows it to attach to multiple KRAS mutation subtypes and block their cancer-promoting activity.
The phase III clinical trial enrolled approximately 500 patients with metastatic pancreatic cancer whose disease had worsened despite earlier treatments.
Participants were randomly assigned either daraxonrasib or standard chemotherapy.
The results were striking. Median overall survival was 13.2 months for patients receiving daraxonrasib. Median overall survival was 6.7 months for those receiving chemotherapy.
Patients on the new drug reported better quality of life and lower pain levels. Tumour shrinkage was observed in a substantial proportion of patients. Patients remained on treatment significantly longer than those receiving chemotherapy.
Researchers noted that many patients were still receiving the drug when the data were analysed, suggesting survival benefits could increase further with longer follow-up.
"Daraxonrasib, a form of targeted therapy that works on a particular pathway (the RAS pathway) that is active in pancreatic cancers, was shown to improve survival to 13.2 months compared to only 6.6 months with chemotherapy. While the absolute numbers may not appear impressive, what is eye-catching is that it is an oral drug as compared to intravenous chemotherapy and also the fact that this is one of the first drugs in this class that has been shown to be active," explains Dr Ramaswamy. He further explains that a whole pipeline of such molecules is being investigated in pancreatic as well as other cancers and sets the stage for further improvements in this, to date, difficult-to-treat cancer. Patients can now look forward to meaningful increases in their lifespans as further research is likely to introduce even better molecules in the future.
Beyond extending survival, researchers highlighted another important finding: patients generally tolerated the treatment better than conventional chemotherapy.
The most commonly reported side effects included skin rash and mouth sores. While some cases were severe enough to require dose adjustments, investigators said the overall side-effect profile compared favourably with chemotherapy.
Could it become the new standard of care?
Experts presenting the data argued that daraxonrasib could soon become the preferred treatment option for patients with previously treated metastatic pancreatic cancer.
The U.S. Food and Drug Administration (FDA) is expected to expedite its review of the drug. Meanwhile, eligible patients are being granted access through the agency's expanded-access programme.
Researchers are already exploring whether the drug could be used earlier in the disease course, including before surgery or in combination with other therapies.
The success of daraxonrasib also reflects broader progress in pancreatic cancer research. Several other KRAS-targeting drugs are currently in development, while researchers are testing personalised vaccines and immunotherapy-based strategies aimed at preventing recurrence after surgery.
For decades, pancreatic cancer has lagged behind other cancers such as lung, breast and melanoma, where targeted therapies have dramatically improved outcomes.
Daraxonrasib may not be a cure. However, experts say the study provides long-awaited evidence that directly targeting KRAS can meaningfully alter the course of a disease that has remained stubbornly resistant to treatment.
