The dawn of RAS-targeted therapy: a landmark breakthrough of daraxonrasib in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies. More than 80% of patients are diagnosed at an advanced stage, and the 5‑year survival rate remains approximately 13% [ 1 , 2 ]. For patients with metastatic PDAC (mPDAC), first-line chemotherapy yields a median overall survival (OS) of less than one year [ 3 , 4 ]. The situation in the second‑line setting is even more discouraging: objective response rates (ORRs) are usually below 10%, median progression‑free survival (PFS) is only 2–3 months, and median OS ranges from 5 to 7 months [ 5 ]. Over the past two decades, more than 20 second‑line clinical trials have been conducted, but nearly all of them have failed. Given the long-standing therapeutic stagnation in this field, the simultaneous publication of two daraxonrasib studies in N Engl J Med marks a historic turning point [ 6 , 7 ].