It was met with a standing ovation. A long and liberating applause at the annual congress of the American Society of Clinical Oncology (ASCO) in Chicago accompanied the presentation of the results of daraxonrasib, an experimental pill that in metastatic pancreatic cancer nearly doubled survival compared to standard chemotherapy. A result described by many experts as the most important in recent decades for a disease that remains one of the deadliest in oncology. Not a definitive cure, but the opening of a path that until a few years ago seemed impassable.
AN UNPRECEDENTED RESULT
The data come from the international phase III RASolute-302 study, which involved 500 patients with metastatic pancreatic adenocarcinoma who had already undergone a previous line of treatment. Participants were assigned to two groups, one treated with daraxonrasib and the other with standard second-line chemotherapy.
The difference observed was clear. Median overall survival increased from 6.7 months in the chemotherapy group to 13.2 months in the group that received the new drug. The risk of death was reduced by 60%, while one year after the start of treatment, 53.2% of patients treated with daraxonrasib were still alive compared to 17.3% of those undergoing conventional therapy.
For Dr. Rachna Shroff of the University of Arizona Cancer Center, who did not participate in the study, these are results that change the therapeutic landscape of the disease. “We are seeing unprecedented survival,” she said. The specialist recounted being moved when reading the data for the first time: “After 16 years spent treating pancreatic cancer, I started crying in the clinic.”
THE COMPANY BEHIND THE DRUG
Behind the development of daraxonrasib is Revolution Medicines, a biotechnology company based in Redwood City, California, specializing in research on targeted therapies against tumors driven by mutations in the RAS family. The company has focused much of its activity on a target that for decades was considered almost unreachable in oncology, namely targeting the RAS proteins responsible for the growth of many aggressive tumors.
Daraxonrasib represents the company’s most advanced program, but the pipeline also includes other experimental drugs directed against specific KRAS variants and other alterations of the same biological pathway. Following the results of the RASolute-302 study, Revolution Medicines has initiated further phase III trials in metastatic pancreatic cancer and other RAS-dependent neoplasms, such as lung and colorectal cancer, aiming to extend the use of the new class of RAS(ON) inhibitors. In the United States, the company has also obtained several regulatory incentives from the Food and Drug Administration to accelerate clinical development and patient access to the drug in advanced pancreatic cancer.
THE TARGET THAT FOR YEARS WAS CONSIDERED UNREACHABLE
The importance of the discovery also lies in the drug’s mechanism of action. Over 90% of pancreatic tumors have alterations in the KRAS gene, one of the main drivers of tumor growth. For decades, scientists considered this protein “undruggable,” meaning impossible to target with specific drugs, due to its particular molecular structure.
Daraxonrasib belongs to a new generation of RAS(ON) inhibitors. The drug, writes The Conversation, does not act like traditional chemotherapy but exploits an innovative mechanism that allows it to indirectly bind to the active KRAS protein and block its proliferation signals. In this way, it interrupts one of the fundamental biological processes that fuel tumor growth.
“The idea of targeting KRAS has always been the Holy Grail of oncology and especially pancreatic cancer,” explained Shroff. “The RAS revolution has arrived, and this study shows that targeting KRAS in pancreatic cancer is possible and effective.”
NOT ONLY SURVIVAL BUT ALSO QUALITY OF LIFE
The benefits observed are not limited to survival duration. The study also showed better disease control, with a doubling of progression-free survival and a significant increase in tumor responses.
According to researchers, about one-third of patients treated with daraxonrasib experienced a reduction in tumor size, a percentage significantly higher than that observed with chemotherapy. Additionally, a positive impact on symptoms and the need for supportive therapies, particularly pain management, was noted.
Chiara Cremolini, national director of the Italian Association of Medical Oncology (Aiom), highlighted how the drug, in addition to prolonging survival, “improves quality of life and reduces the need for pain therapy,” also emphasizing the overall good tolerability of the treatment and the possibility of oral administration. The expert also noted that clinical experience in the Italian centers involved in the trial confirms a manageable side effect profile, mainly represented by skin rash and stomatitis, and identified the result as a possible starting point for future therapeutic strategies, aiming to anticipate the use of the drug in earlier stages of the disease.
Overall, serious adverse events occurred less frequently than with chemotherapy, with severe toxicities reported in 43.6% of patients treated with daraxonrasib versus 57.5% of those undergoing standard therapy. Definitive treatment discontinuations were also less frequent in the group receiving the new drug.
WHY IT CANNOT YET BE CALLED A CURE
However, the enthusiasm sparked by the results is accompanied by a constant clarification from specialists. Daraxonrasib does not represent a cure for pancreatic cancer.
The disease, as explained by Fondazione Veronesi, remains extremely complex, and many patients develop resistance mechanisms over time that allow tumor cells to resume growth. Moreover, not all study participants experienced the same benefit, and survival, although significantly improved, remains limited to just over a year in previously treated metastatic forms.
“We are not facing a cure, but a huge step forward,” emphasized oncologist Zev Wainberg of the University of California, one of the study authors, highlighting how the result primarily represents concrete proof of the possibility to effectively target the main biological driver of the disease.
THE NEXT CHALLENGE
Researchers are already evaluating the use of the drug in earlier stages of the disease and in combination with other therapies. The goal is to verify whether benefits can be further expanded by using daraxonrasib as a first-line treatment or in combination with other targeted and immunotherapeutic approaches.
In the United States, the Food and Drug Administration has authorized an expanded access program for some patients and is reviewing the regulatory dossier through an accelerated procedure. In Europe, the drug has obtained orphan drug designation but is not yet available in clinical practice. If the process proceeds without delays, possible European approval could come in 2027.
THE NUMBERS OF THE DISEASE
Pancreatic cancer is a relatively less frequent disease compared to other neoplasms but has an extremely high impact in terms of mortality. Globally in 2022, approximately 510,000 new cases and over 470,000 deaths were recorded, indicating overall very low survival and a disease that nearly matches diagnosis and deaths in the same year in numbers.
In Italy, the most recent estimates indicate over 13,000 new cases per year, with an almost equal distribution between men and women. The number of people living after diagnosis is about 23,000, a modest number compared to other more common neoplasms but linked to the unfavorable prognosis of the disease. Survival, states Airc, remains among the lowest in oncology: five-year survival is around 11–12% depending on sex, reflecting the difficulty of treatment especially in advanced stages.
