FDA approves first RAS-targeted therapy for metastatic pancreatic cancer
· News-MedicalThe U.S. Food and Drug Administration (FDA) has approved daraxonrasib, an oral multi-selective RAS(ON) inhibitor, for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy. The approval is based primarily on the results from the pivotal randomized phase 3 RASolute 302 trial comparing daraxonrasib to chemotherapy as second-line therapy for patients with metastatic pancreatic cancer, led by Brian Wolpin, MD, MPH, director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute.
Brian Wolpin, MD, MPH, Director, Gastrointestinal Cancer Center, Dana-FarberFor many years, researchers believed that successfully targeting RAS had the potential to transform the treatment of pancreatic cancer, but therapeutically blocking RAS signaling proved extraordinarily challenging. The FDA approval of daraxonrasib represents a landmark advance for patients with metastatic pancreatic cancer. The nearly doubling of median overall survival time seen with this targeted treatment represents meaningful progress for patients where new treatment options are urgently needed."
Daraxonrasib is the first approved targeted therapy in pancreatic cancer designed to inhibit RAS, the major cancer-driving pathway in the disease. It works as a molecular glue that together with another protein, cyclophilin A, blocks the signaling of RAS proteins. More than 90 percent of patients with pancreatic cancer have cancer-driving mutations in the KRAS oncogene within the RAS family of genes.
Patients who received daraxonrasib showed a substantial improvement in overall survival compared to those treated with chemotherapy. In the overall study population, daraxonrasib reduced the risk of death by 60%, with a hazard ratio of 0.40. Median overall survival was 13.2 months with daraxonrasib compared to 6.7 months with chemotherapy. There was also a reduction in the risk of cancer progression observed among these patients, with a median progression-free survival of 7.2 months compared to 3.6 months with chemotherapy.
In the overall study population of the phase 3 RASolute 302 study, the objective response rate was 31.6 percent with daraxonrasib and 11.2 percent with chemotherapy. Among patients with a known RAS G12 mutation, 33.2 percent of those who received daraxonrasib experienced substantial tumor shrinkage or disappearance compared to 11.8 percent of those receiving chemotherapy.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and one of the deadliest forms of cancer. About 65,000 people in the United States are diagnosed with PDAC each year, and more than 50,000 die from the disease despite current standard treatments. Because pancreatic cancer often causes few or no symptoms in its early stages, about 80% of patients are diagnosed after the cancer has invaded tissues around the pancreas or spread to other parts of the body, when treatment options are more limited. For patients with metastatic pancreatic cancer, the five-year relative survival rate is approximately 3% in the United States.
"For patients and families facing metastatic pancreatic cancer, this approval represents an advance that has been long awaited and long deserved. It shows how relentlessly studying the biology of cancer leads to new treatments that help patients, even for the most difficult to treat of cancer types. The future is now filled with promise, as the Hale Center team and the field at large build on this approval to identify further approaches that provide durable disease responses and more cures. This is an unprecedented time, and we look forward to the daraxonrasib approval heralding the start of a new era in pancreatic cancer treatment," said Wolpin.
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