Dr Pant on Managing Toxicities With Daraxonrasib in PDAC

"Once we get more patients on [studies with daraxonrasib], we can learn to take care of these AEs or uncover other AEs that we haven’t seen so much at this point.”

Shubham Pant, MD, MBBS, a professor in the Department of Gastrointestinal (GI) Medical Oncology and director of Clinical Research at The University of Texas MD Anderson Cancer Center, shared insights into the safety profile and clinical management of the RAS(ON) multi-selective inhibitor daraxonrasib (RMC-6236) in pancreatic ductal adenocarcinoma (PDAC).

Daraxonrasib has shown significant efficacy in previously treated metastatic PDAC, based on data from the phase 3 RASolute 302 trial (NCT06625320), as well as promising efficacy signals in the first line based on phase 1/2 data (NCT05379985; NCT06445062).

Although the therapeutic potential of daraxonrasib is significant, Pant noted that its use is associated with a distinct set of toxicities that require proactive management. The primary adverse effect (AE) observed with this agent is a dermatologic rash, which occurs in approximately 90% of patients. Although highly prevalent, the majority of these cases are manageable; grade 3 or 4 rashes, which involve a higher percentage of body surface area, are reported in only 10% to 15% of the patient population, he asserted. In instances of severe rash, clinical protocols typically necessitate holding the drug or implementing dose modifications. Pant emphasized that oncologists have become increasingly proficient at managing these dermatologic AEs over the several years the drug has been in clinical development.

Beyond dermatologic AEs, the safety profile includes GI toxicities, such as nausea and diarrhea, as well as stomatitis. Pant observed that as more patients are treated, medical teams will continue to refine their ability to mitigate these AEs and potentially uncover less frequent toxicities. Ultimately, the safety profile of daraxonrasib is considered manageable and consistent with previous data. By balancing potent RAS(ON) inhibition with established management strategies, oncologists can optimize the delivery of this potentially practice-changing therapy, he concluded.