Study: New pancreatic cancer drug doubled survival time
The fight against deadly pancreatic cancer took a positive turn this spring with a study finding a new drug can help patients live longer.
The New England Journal of Medicine (JAMA) published the study showing daraxonrasib taken daily as a pill helped metastatic pancreatic cancer patients live for a median of 13.2 months compared with 6.7 months for those being treated with chemotherapy. The findings are groundbreaking, as pancreatic cancer is one of the deadliest types of cancer with the five-year overall survival rate at only 13%. It is extremely difficult to detect before it starts spreading to other organs. The American Cancer Society estimates it will kill more than 52,000 Americans this year.
“Pancreatic cancer has an overall poor prognosis since it is usually diagnosed at an advanced stage,” says Dr. Dulabh Monga with the AHN Cancer Institute. “There are no effective screening tests that can diagnose this cancer at an early stage. Pancreatic cancer has an aggressive biology and surrounds itself with an impenetrable desmoplastic stroma that does not allow chemotherapy to effectively penetrate and destroy the cancer cells.”
For decades, that meant that protein was considered “undruggable.” This new medication uses what is described as a sort of molecular glue to bind with many KRAS subtypes.
How does it work?
Daraxonrasib is a daily pill that can now bind to the protein that fuels tumor growth.
“The driver mutation for 90% of pancreatic cancers is KRAS,” explains Monga. “Healthy KRAS genes regulate and maintain cell division through an ‘on and off’ switch. In pancreatic cancers, the KRAS gene remains in the ‘on’ position, resulting in uncontrolled cell division that promotes tumor formation.”
The study and trial looked at metastatic pancreatic cancer patients who had progressed on first-line chemotherapy but had stopped responding. The daily pills not only nearly doubled survival time, but patients also reported fewer severe side effects than with chemotherapy.
“Results represent a 60% reduction in the risk of death,” says Monga. “These benefits were consistent for patients with RAS G12 mutations as well as the broader intent-to-treat population. This drug has manageable side effects that are not as severe as chemotherapy-related toxicities. Patients receiving daraxonrasib had sustained better overall global quality of life.”
The study shows effectiveness of the drug eventually falls off, but patients taking it reported less pain and a better quality of life during treatment.
Who can it help?
The next step is for creator Revolution Medicines to submit research data on darazonrasib to the U.S. Food and Drug Administration (FDA) for approval. There are ongoing clinical trials testing daraxonrasib in earlier metastatic settings with early results of these trials being quite encouraging. The good news is that darazonrasib could help a great number of pancreatic cancer patients.
“A metastatic pancreatic cancer patient who has progressed on first-line chemotherapy and has a RAS mutation is eligible for this drug,” Monga says.
There is also more good news about research being done close to home in Pittsburgh.
“I am excited to report that we have just opened a clinical trial at AHN Cancer Institute, sponsored by Astellas,” Monga said. “This is a Phase 3, double-blind, placebo-controlled, randomized study to assess the efficacy and safety of ASP3082 in combination with mFOLFIRINOX or NALIRIFOX as first-line treatment in participants with KRAS G12D-mutated metastatic pancreatic adenocarcinoma.”
The KRAS G12D is seen in 45% of patients with pancreatic cancer. The takeaway is that patients facing a pancreatic cancer diagnosis should ask their doctors about new clinical trials and new treatments.
“All patients with a pancreatic cancer diagnosis should make sure their physician orders next-generation sequencing that tests for the RAS mutation subtype,” says Monga. “Those interested can reach out to 412-578-HOPE (4673).”