RASolute 302 Design and Study Populations

The phase 3 RASolute 302 trial randomly assigned 500 patients with metastatic pancreatic cancer and progression on 1 prior regimen to oral daraxonrasib 300 mg once daily or investigator's choice of 4 standard chemotherapy regimens. Tanios S. Bekaii-Saab, MD, outlines eligibility, including Eastern Cooperative Oncology Group performance status of 0 or 1, measurable disease, and documented RAS mutational status, with wild-type tumors included. Shiraj Sen, MD, PhD, calls the comparator clinically relevant, since a fixed arm could have forced chemotherapy rechallenge, and notes that daraxonrasib doubled overall and progression-free survival vs pooled chemotherapy; questions about individual chemotherapy arms remain open. Paul E. Oberstein, MD, finds the physician's choice design generalizable, because most patients received 1 of 2 regimens dictated by first-line therapy. He recalls that more than 90% of participants had RAS G12 mutations and that small subgroup numbers limit interpretation for other patients. Based on current knowledge, Dr. Oberstein would still consider daraxonrasib for a patient with RAS wild-type disease.