Daraxonrasib for Pancreatic Cancer: A Revolutionary Breakthrough

Pancreatic cancer is widely known to be one of the most aggressive forms of cancer. In the United States, it is the fourth leading cause of cancer-related deaths. Pancreatic ductal adenocarcinoma, abbreviated PDAC, is the most common form of pancreatic cancer, accounting for over 90% of all cases. PDAC is also most often diagnosed at advanced stages, and consequently, has a 5-year survival rate of less than 10%. This percentage is even lower in those with metastatic PDAC.

Unique combinations of genetic mutations, which are structural alterations in the DNA of living organisms, are known to characterise several forms of cancer. One such mutation is KRAS (Kirsten rat sarcoma virus oncogene homologue), which is found in over 90% of all PDACs. KRAS is a kind of RAS mutation; the RAS genes control cell growth and division, and therefore, a mutation in these genes results in uncontrolled cell division. RAS mutations are also known to contribute to the development of metastases in pancreatic and other cancers.

KRAS mutations have been considered an impossible therapeutic target for decades. That is, until Revolution Medicines announced the results of a phase 3 clinical trial with the drug daraxonrasib earlier this month. Through this trial, the researchers found evidence that the drug could potentially almost double overall survival outcomes in patients with metastatic PDAC.

The trial was designed to evaluate the efficacy and safety of the drug as the only treatment in patients with previously treated metastatic PDAC. Trial participants, who were patients with metastatic PDAC characterised by a wide range of RAS mutations, were administered either 300 mg daraxonrasib or the investigator’s choice of standard chemotherapy.

The median overall survival rate was found to be 13.2 months with daraxonrasib versus 6.7 months with just chemotherapy. While a 6-month improvement may appear modest at first, it is a significant breakthrough when considering the low survival rate for metastatic PDAC. The principal investigator on the trial, Biran M. Wolpin, MD, remarked, “For patients with metastatic pancreatic cancer, new treatment options are urgently needed to increase survival time and improve quality of life.”

Following the trial, researchers must present their data to the United States Food and Drug Administration (FDA). Upon receiving FDA approval, the drug will be made available for the treatment of patients with metastatic PDAC who have received prior treatment. Daraxorasib has been selected for the FDA Commissioner’s National Priority Voucher pilot program to expedite the review and approval process.

The breakthrough is also meaningful for the treatment of other RAS-affected cancers. “We believe these results firmly validate our pioneering approach to targeting common RAS-addicted cancers through RAS(ON) inhibition,” noted Mark A. Goldsmith, MD, PhD, who is the chief executive officer and chairman of Revolution Medicines.