Daraxonrasib for Pancreatic Cancer: A Q&A with Dana-Farber’s Brian Wolpin, MD, MPH 

The U.S. Food and Drug Administration has approved daraxonrasib for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy.  

“This is an exceptional moment for patients with pancreatic cancer,” says Brian Wolpin, MD, MPH, director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute, who led the pivotal clinical trial supporting of the approval. “The FDA approval is an important step toward making daraxonrasib broadly available to the patients who could benefit from it.” 

Why is the approval of daraxonrasib such an important advance for patients with metastatic pancreatic cancer? 

Wolpin: For patients with metastatic pancreatic cancer, this approval represents something we haven’t had enough of: a new treatment that meaningfully improves outcomes by targeting the biology of the cancer. It is a tremendous day for patients and their families. 

It also gives researchers a critical foothold to build on. Now that we have demonstrated that we can successfully target KRAS in pancreatic cancer, we have an opportunity to expand on that knowledge, understand the biology even more deeply and develop new approaches that could make an even greater difference for patients in the years ahead. 

What makes daraxonrasib different from other treatments? 

Wolpin: For decades, we have known that KRAS mutations are a major driver of pancreatic cancer, but KRAS has been extraordinarily difficult to target with medicines. We’ve known the target was there, but we haven’t had an effective way to go after it in the clinic.  

Daraxonrasib changes that. It gives us a new way to target the different KRAS mutations found in pancreatic cancer and represents an important advance for patients with a disease where we’ve had far too few effective treatment options. 

What is the evidence that supports this approval? 

Wolpin: This FDA approval is based on the results of the phase 3 RASolute 302 trial. These results are meaningful because they represent the most significant therapeutic advance we’ve seen in metastatic pancreatic cancer in decades.  

Historically, patients whose disease progressed after first-line chemotherapy have had very limited treatment options and poor outcomes. The RASolute 302 trial provided definitive evidence that daraxonrasib could improve outcomes compared with the chemotherapy we have traditionally used after a patient’s first treatment for metastatic pancreatic cancer.  

Daraxonrasib, when compared to the subsequent chemotherapy, improved multiple measures of benefit, including nearly doubling how long patients lived, and improving how long their cancer remained controlled, the degree of tumor shrinkage and their quality of life. To see improvements across all of these measures is particularly encouraging. 

Does daraxonrasib cause side effects? 

Wolpin: Like any cancer treatment, daraxonrasib can cause side effects. The most common include an acne-like rash, often on the face, chest or back, as well as inflammation of the mouth and gastrointestinal tract, which can cause mouth sores or nausea. We are learning more about how to prevent and manage these effects, and overall, patients in the RASolute 302 trial experienced fewer side effects with daraxonrasib than with chemotherapy. 

Is daraxonrasib a cure for metastatic pancreatic cancer? 

Wolpin: It’s important to be clear that daraxonrasib is not a cure for metastatic pancreatic cancer. Most patients with metastatic disease will ultimately develop resistance, meaning the cancer finds a way to grow despite treatment.  

That is why an important area of research now is understanding how that resistance develops and finding ways to prevent or overcome it. Our hope is that by combining daraxonrasib with other approaches, we can make responses more durable and continue to improve outcomes for patients. 

What research is being done to continue improving pancreatic cancer treatment? 

Wolpin: We have a tremendous number of studies underway to understand how pancreatic cancers develop resistance to daraxonrasib and other RAS-targeted therapies. If we can identify the mechanisms that allow cancer cells to escape treatment, we can begin designing new strategies to block those mechanisms. That work could ultimately lead to longer and more durable responses for patients.