The US Food and Drug Administration (FDA) has approved a drug for advanced pancreatic cancer following a phase 3 clinical trial in which patients lived twice as long as those who were treated with chemotherapy.
Pancreatic cancer is one of the deadliest cancers, with almost 500,000 deaths registered worldwide in 2022. Since there are no effective screening tests and it rarely causes noticeable symptoms, it’s usually detected at advanced stages of the disease, when the cancer has already spread to other tissues. Only 3% of patients with advanced pancreatic cancer live longer than five years.
The drug, called daraxonrasib, developed by the US company Revolution Medicines, acts by shutting off a gene called KRAS. KRAS is altered in more than 90% of pancreatic cancers and up to 30% of all cancers and drives cancer growth. In the phase 3 clinical trial with 500 participants with advanced pancreatic cancer, patients lived on average 13.2 months when taking only daraxonrasib daily, comparing to 6.7 months for those being treated with chemotherapy.
Daraxonrasib’s potential to treat cancer has been studied extensively in animals, including mice implanted with patient-derived tumours carrying KRAS mutations. Researchers have also studied daraxonrasib in combination with approved cancer therapies, such as anti-PD-1, CDK4/6 inhibition and anti-CTLA-4, in mice to evaluate the potential of combined therapies to circumvent resistance to daraxonrasib. In another study, mice, rats, dogs and cynomolgus monkeys were also used to study how the drug behaved in the body, including its absorption and availability after oral administration. Monkeys were further used to assess drug safety before being administered in humans.
“Moving forward, we expect to see an increase in clinical trials exploring combination therapies, pairing KRAS inhibitors such as daraxonrasib with other drugs to prevent tumors from developing resistance and to extend survival even further,” wrote Christopher Lieu, a medical oncologist from the University of Colorado Anschutz, on The Conversation.