Dr Pant on the Importance of Targeted Therapy and Mutation Testing in Pancreatic Cancer

“It is very important that all patients with metastatic [or] advanced pancreatic cancer should undergo mutation testing or next-generation sequencing.”

Shubham Pant, MD, MBBS, professor, Department of Gastrointestinal (GI) Medical Oncology, Department of Investigational Cancer Therapeutics (Phase I Center), The University of Texas MD Anderson Cancer Center, discusses the need for next-generation sequencing (NGS) in patients with advanced, metastatic pancreatic cancer, highlighting the importance of targeting RAS mutations in this patient population.

Notably, Pant delved deeper into these takeaways in a presentation at a symposium hosted by the Ruesch Center for the Cure of Gastrointestinal Cancers at Georgetown University.

Biomarker testing plays a critical role in the management of pancreatic cancer, particularly for patients with advanced or metastatic disease, Pant begins, stating that conducting mutation testing or NGS is highly recommended for these patients. This approach enables the identification of RASmutations and other actionable alterations, opening pathways for clinical trial enrollment or targeted therapies, he shares. Beyond RAS mutations, other genetic alterations, such as BRCA1/2mutations, can guide treatment with approved options like Olaparib (Lynparza). Additionally, some patients with pancreatic cancer may have rare alterations, such as RET fusions, microsatellite instability–high status, or NTRK fusions, Pant explains. Without testing, these actionable mutations remain undetected, underscoring the necessity of NGS for patients with advanced pancreatic cancer, he adds.

Currently, no approved therapies specifically target RAS mutations in pancreatic cancer, Pant continues; however, significant progress is being made in clinical trials exploring novel RAS inhibitors. One promising agent, RMC-6236, is a RAS(ON) inhibitor that targets the active state of RAS proteins. This drug has rapidly advanced in pancreatic cancer research and is being evaluated as a second-line treatment for pancreatic cancer compared with standard of care, he reports. Although these therapies are not yet approved, they represent a hopeful step forward in the treatment paradigm for patients with RAS mutations, according to Pant. Continued innovation and clinical research may soon bring effective treatment options to this challenging-to-manage subset of pancreatic cancer, Pant concludes.