The U.S. Food and Drug Administration approved a first-in-class pill Wednesday for certain patients with metastatic pancreatic cancer after a Phase III trial found that the treatment nearly doubled median survival compared with standard chemotherapy.
Rasonque, known generically as daraxonrasib, is approved for adults with metastatic pancreatic adenocarcinoma who have received at least one previous systemic therapy or are not candidates for multiagent systemic therapy.
Daily Pill Targets Major Cancer Driver
Rasonque is taken once daily and targets multiple forms of RAS, a family of proteins involved in regulating cell growth. Mutations that leave RAS proteins continuously active can drive uncontrolled tumor growth.
Oncogenic RAS mutations are present in more than 90% of pancreatic ductal adenocarcinomas, according to the peer-reviewed Phase III study published in The New England Journal of Medicine.
Researchers had long considered RAS proteins difficult to target effectively with medication. The FDA described Rasonque as the first RAS-targeted treatment approved for metastatic pancreatic cancer.
“Today’s approval provides a critical new option for patients facing an extraordinarily difficult and historically hard-to-treat cancer,” Acting FDA Commissioner Kyle Diamantas said in the agency’s announcement.
The approval applies to adults whose pancreatic adenocarcinoma has spread to other parts of the body and who have already received systemic treatment. It can also be prescribed when physicians determine that a patient cannot receive a multiagent treatment regimen.
Rasonque is not approved for all pancreatic cancers or as a first-line treatment for every newly diagnosed patient.
Trial Finds Significant Survival Difference
The approval was supported by the RASolute 302 trial, an international, randomized, open-label study involving 500 adults with previously treated metastatic pancreatic ductal adenocarcinoma.
Researchers assigned 248 patients to receive daraxonrasib and 252 to receive chemotherapy selected by the treating investigator.
Median overall survival reached 13.2 months among patients receiving daraxonrasib, compared with 6.7 months in the chemotherapy group.
Median progression-free survival—the period during which the cancer did not worsen—was 7.2 months with daraxonrasib and 3.6 months with chemotherapy.
Both differences were statistically significant, according to the published trial results.
The international investigator group included Dr. Shubham Pant of the University of Texas MD Anderson Cancer Center in Houston.
The findings do not mean that every patient will live for 13.2 months or that the drug cures metastatic pancreatic cancer. Median survival identifies the point at which half the patients in a study remain alive and half have died. Individual outcomes can vary.
The trial was open-label, meaning patients and investigators knew which treatment participants received. Revolution Medicines, the company that developed Rasonque, funded the study.
Side Effects Remain a Consideration
The FDA listed the drug’s most common side effects as rash, diarrhea, inflammation of the mouth, nausea, fatigue, vomiting, abdominal pain, swelling, decreased appetite, and bleeding.
Grade 3 or higher adverse events occurred in 61.8% of patients receiving daraxonrasib and 69.6% of patients receiving chemotherapy.
Treatment-related side effects caused 1.2% of patients in the daraxonrasib group to discontinue treatment, compared with 11.2% in the chemotherapy group, according to the published study.
Patients and oncologists will need to weigh the potential survival benefit against the medication’s risks, the patient’s condition, previous treatments, and available alternatives.
Approval Arrives Months Ahead of Schedule
The FDA approved Rasonque approximately 6½ months before its scheduled user-fee deadline.
The agency previously granted the drug Breakthrough Therapy, Orphan Drug, and Priority Review designations. The application was also reviewed through the Commissioner’s National Priority Voucher pilot program, which is intended to expedite treatments addressing significant public health priorities.
In May, the FDA authorized an expanded-access protocol that allowed eligible patients to receive daraxonrasib before its formal approval. Licensed U.S. physicians were required to request access on behalf of eligible patients.
Revolution Medicines is also studying daraxonrasib alone and in combination with chemotherapy as a potential first-line treatment for metastatic pancreatic cancer. The ongoing Phase III trial is expected to enroll approximately 900 patients who have not previously received systemic therapy for metastatic disease.
Those first-line uses have not been approved.
Treatment and Prevention Efforts Advance
Approximately 67,000 Americans are diagnosed with pancreatic cancer annually. Between 90% and 95% of those cases are pancreatic adenocarcinoma, according to the FDA.
The disease is particularly dangerous because it is frequently discovered after it has spread, when surgery may no longer be an option.
The approval comes amid broader efforts to target the genetic mutations that drive pancreatic tumors.
As previously reported by The Dallas Express, an experimental vaccine targeting common KRAS mutations recently generated lasting immune responses in 90% of 20 high-risk participants in a Phase I trial.
That vaccine is being studied as a possible way to prevent or intercept pancreatic cancer before it develops and remains experimental. Rasonque addresses a different stage of the disease by treating pancreatic cancer that has already spread.
The FDA’s approval provides a new option for eligible patients while researchers investigate whether RAS-targeted treatments could also benefit patients earlier in the disease.
Provided by Dallas Express
