Newly Approved Pancreatic Cancer Treatment Has Been Shown To Prolong Life — And Highlights Siteman’s Role in Bringing Innovation to Patients
FDA approves first-in-class drug trialed at WashU Medicine and Siteman Cancer Center — a new option for patients with metastatic disease
Daraxonrasib is a drug that targets RAS proteins, which are mutated in more than 90% of pancreatic cancers.
As a clinical trial site, Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine evaluated the targeted therapy and offered it to qualified patients before it was widely available elsewhere. Today’s announcement from the FDA makes daraxonrasib standard of care for adults with metastatic PDAC who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy.
Kian-Huat Lim, MD, PhD, director of gastrointestinal oncology at WashU Medicine and a nationally recognized specialist in pancreatic cancer care and research at Siteman Cancer Center, served as site principal investigator for the international Phase 3 RASolute 302 clinical trial evaluating daraxonrasib.
Siteman also was among the first centers in the U.S. earlier this year to offer daraxonrasib as part of an FDA-authorized expanded-access program for certain patients with previously treated metastatic PDAC. Prior to that, the FDA had granted Breakthrough Therapy and Orphan Drug designations, as well as placed daraxonrasib on its Priority Review list.
In the late-stage trial offered at Siteman and other sites, patients whose pancreatic cancer had progressed after initial chemotherapy were randomly assigned to receive daraxonrasib or a second round of chemotherapy. Patients receiving daraxonrasib had a median overall survival of 13.2 months, compared with 6.7 months for those receiving the additional chemotherapy. The study also found that nearly one-third of patients experienced substantial tumor shrinkage.
“We are prolonging life in patients who previously had no other good option other than another rather toxic chemotherapy with limited efficacy or clinical trials,” Lim said of the results.
The FDA announced the approval “months ahead of schedule,” according to its announcement. Angelo de Claro, MD, director of the FDA’s Oncology Center of Excellence, said, “This drug showed unprecedented results in an area of high unmet need.”
Daraxonrasib is taken once daily in pill form. Common side effects include rash, mouth sores, diarrhea and fatigue, and some patients require treatment interruptions because of the severity of those effects.
Siteman One of Only Three Specialized Programs of Research Excellence (SPOREs) in Pancreatic Cancer in the U.S.
The availability of daraxonrasib at Siteman Cancer Center reflects more than access to a promising new therapy. It is a product of Siteman and WashU’s longstanding commitment to pancreatic cancer research and the ability of multiple researchers to make discoveries in the laboratory and rapidly translate promising results into clinical care.
The Pancreatic Cancer Specialized Program of Research Excellence (SPORE) at WashU Medicine and Siteman is one of only three pancreatic cancer SPOREs in the country, as designated by the National Cancer Institute. The SPORE brings together researchers and clinicians across disciplines to develop new approaches to treat pancreatic cancer, which is now the third-leading cause of cancer-related deaths in the U.S.
Research within the SPORE spans immunotherapy, targeted therapies, vaccines and multi-modality treatments, in addition to investigations into drug resistance and other strategies to better treat pancreatic tumors. Among the investigators is Lim, whose laboratory is studying how pancreatic cancer cells survive chemotherapy and whether blocking the MK2 protein can make tumors more vulnerable to treatment. The work is advancing toward clinical testing.
David DeNardo, PhD, director of the pancreatic cancer SPORE at WashU Medicine and Siteman, is investigating ways to overcome treatment resistance through inhibiting FAK kinase, which stimulates the immune system to attack pancreatic cancer. Other researchers, including William Gillanders, MD, are exploring neoantigen vaccines, and Sana Karam, MD, PhD, chief of the Department of Radiation Oncology, is testing radiation combined with immune modulators. Several other investigators here also are working on different novel drug combinations.
Siteman has a large portfolio of trials specific to pancreatic cancer, including a substantial number of investigator-initiated trials (IITs) using different forms of new KRAS inhibitors with fewer side effects, giving physicians and researchers opportunities to test their own discoveries and translate promising laboratory findings into new treatments. In addition, clinical trials using daraxonrasib in combination with newer agents are being developed.
“We are national leaders in investigator-initiated trials, and we have proven results as scientists and clinical trialists,” Lim said. “In addition, we see many patients from throughout the region who are diagnosed with pancreatic cancer. In other words, we have the expertise as clinicians to care for these patients and the ability to offer them the latest options.”
WashU radiation oncologists and medical physicists at Siteman are also worldwide pioneers in developing and advancing the use of real-time adaptive MRI-guided stereotactic body radiation therapy (SBRT) to treat pancreatic cancer. The technology enables patients to receive high-dose, precision-targeted radiation therapy, which has been shown to extend survival in some patients.
Because of increased options, Lim said that patients who are now diagnosed with pancreatic cancer should be more hopeful.
“We have promising research underway here that could point the way to even more effective treatment options,” he said. “The good news is that we’ve already moved the needle and we now have multiple ways to tackle this cancer.”
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