An experimental drug has roughly doubled survival in patients with one of the deadliest of all common cancers, according to results from a large international trial presented at the American Society of Clinical Oncology meeting in Chicago, raising hopes of a genuine shift in the treatment of pancreatic cancer. In the phase 3 RASolute 302 study, the oral RAS inhibitor daraxonrasib extended median overall survival to 13.2 months, compared with 6.7 months for patients given chemotherapy.
The trial enrolled 500 patients with metastatic pancreatic cancer who had already been treated once before, randomly assigning them to receive either daraxonrasib or chemotherapy chosen by their physician. Alongside the survival benefit, which carried a hazard ratio of 0.40, the drug doubled the time before the disease worsened — median progression-free survival of 7.2 months against 3.6 months — and shrank tumours in 31.6% of patients, compared with 11.2% on chemotherapy.
Pancreatic cancer is notoriously difficult to treat. It is frequently caught late, responds poorly to existing therapies and has among the lowest five-year survival rates of any malignancy. The disease is driven in the overwhelming majority of cases by mutations in the RAS family of genes, a target that frustrated drug developers for decades before a recent wave of inhibitors began to make it tractable.
Brian Wolpin of the Dana-Farber Cancer Institute, who presented the findings, described daraxonrasib as the first RAS inhibitor to be evaluated in a large randomised trial in pancreatic cancer. The drug, developed by Revolution Medicines, is a so-called multi-selective RAS(ON) inhibitor designed to block several mutant forms of the protein at once rather than a single variant.
The drug also appeared easier to tolerate than chemotherapy. Treatment-related side effects severe enough to force patients to stop were reported in 1.2% of those on daraxonrasib, against 11.2% in the chemotherapy group, with investigators reporting no unexpected safety signals over the course of the study.
Researchers cautioned that median survival of just over a year still falls far short of a cure, and that longer follow-up and regulatory review lie ahead before the drug could enter routine use. The US Food and Drug Administration granted Revolution Medicines permission in May to open an expanded-access programme for previously treated patients, and the trial results are expected to underpin an application for full approval.