Dr Pant on Managing the Safety Profile of Daraxonrasib in Pancreatic Cancer

Shubham Pant, MD, MBBS, professor in the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at UT MD Anderson Cancer Center, discusses the safety profile of daraxonrasib (Rasonque) and how his team manages its most common toxicities in patients with metastatic pancreatic adenocarcinoma.

Daraxonrasib, an oral RAS(ON) inhibitor, was approved by the FDA in August 2026 for adults with metastatic pancreatic adenocarcinoma who have received at least one prior line of systemic therapy or who are not candidates for multiagent chemotherapy, based on findings from the phase 3 RASolute 302 trial. The recommended dose is 300 mg orally once daily.

Pant explains that the most frequently reported adverse effects include rash, stomatitis, diarrhea, nausea, and paronychia, but notes that most of these toxicities can be managed proactively rather than requiring treatment discontinuation. For dermatologic toxicity, his team starts patients on prophylactic doxycycline at treatment initiation, along with hydrocortisone cream for facial rash and triamcinolone cream for the body. Patients who develop stomatitis are given mouthwashes—either a compounded "magic mouthwash" or a dexamethasone rinse—to reduce mouth sores.

When patients experience intolerable side effects despite these supportive measures, Pant says the standard approach is to hold daraxonrasib temporarily. In his experience, toxicities typically resolve within one to two weeks, after which patients can resume treatment at the same dose or a reduced dose.

Pant's comments underscore that with appropriate prophylaxis and dose management, the adverse effect profile of daraxonrasib is largely manageable, supporting its use as a treatment option for patients with metastatic pancreatic adenocarcinoma following prior systemic therapy.

Read the full interview with Dr Pant.