Once-daily pill doubles survival in pancreatic cancer after chemo fails
Pancreatic cancer has long been a near-certain death sentence, with just 3% of patients living 5 years past diagnosis. Now a new once-daily pill has seen patients live nearly twice as long after chemotherapy fails.
The FDA approved daraxonrasib — sold as Rasonque — on August 26 for metastatic pancreatic adenocarcinoma, making it the first RAS-targeted therapy ever approved for pancreatic cancer. Manufacturer is Revolution Medicines.
The approval was based on the pivotal Phase 3 RASolute 302 trial led by Dr. Brian Wolpin of Dana-Farber Cancer Institute. The study randomized 500 patients who had received prior chemotherapy to either daraxonrasib or standard chemo.
Patients who took daraxonrasib lived a median of 13.2 months, versus 6.7 months for those on chemotherapy — nearly double — and cut risk of death by 60%. Progression-free survival also doubled, to 7.2 months vs 3.6 months.
The data was presented at the American Society of Clinical Oncology annual meeting in Chicago in May. Attendees stood and applauded, some with tears, reports said — a rare sight at a scientific meeting.”I have not seen anything like that before in trials we have run in pancreatic cancer. I just kept repeating, ‘Wow,'” Wolpin said.
The drug works by targeting KRAS, mutated in over 90% of pancreatic cancers. For decades KRAS was thought “undruggable” because of its smooth surface. Daraxonrasib acts as a molecular glue — binding to cyclophilin A and to the active RAS(ON) protein to form a tri-complex that blocks signaling and kills the cancer cell.
It is not a cure, but doctors call it paradigm-shifting.”This is probably the most exciting study that has been reported in pancreas cancer in the last 30, 40 years, if not forever,” said Dr. Anton Bilchik of Providence Saint John’s Cancer Institute.
The approval is for adults who have received at least one prior systemic therapy or who are not candidates for multi-agent chemo, and does not require a specific RAS mutation test because it is multi-selective.
In one case from the trial, a man in his 70s whose cancer had spread to lymph nodes saw tumors shrink so much they became undetectable on scans and remains alive since 2022.
Researchers say dozens of other KRAS-inhibiting drugs are now in testing for pancreatic, colon and lung cancers — all cancers that rely on KRAS — alone and in combination with chemotherapy and immunotherapy.
