FDA Approval Marks New Era for Pancreatic Cancer Treatment

The U.S. Food and Drug Administration has approved the first targeted therapy designed to treat the RAS mutations that drive the vast majority of pancreatic cancers, marking a major advance for patients with metastatic disease.

Daraxonrasib was approved for adults with metastatic pancreatic adenocarcinoma who have received at least one previous systemic therapy or who are not candidates for multiagent systemic therapy.

The approval is based on a randomized clinical trial that showed daraxonrasib nearly doubled median overall survival compared with standard chemotherapy, from 6.7 months to 13.2 months.

For Ignacio Garrido-Laguna, MD, PhD, chair of the Early Therapeutics Development at Moffitt Cancer Center, the approval represents a milestone decades in the making.

“With the recent approval of daraxonrasib, we have for the first time a drug that is able to target the most prevalent genetic alteration that we see in nearly every pancreatic cancer patient, with a prevalence of 90%,” Garrido-Laguna said.

Nearly Doubling Overall Survival

The magnitude of the survival benefit is particularly significant in a disease where treatment options become increasingly limited after cancer progresses.

Ignacio Garrido-Laguna, MD, PhD

“The efficacy data showed that overall survival with daraxonrasib in the second-line setting increased from around six months to over 13 months,” Garrido-Laguna said. “This is a doubling of overall survival.”

To put that into perspective, Garrido-Laguna says median overall survival with some of the best chemotherapy regimens used as initial treatment is around 11 months. That means survival observed with daraxonrasib after a patient's cancer has already progressed compares favorably with outcomes historically seen when patients first begin treatment.

Targeting a Long-Elusive Driver

Daraxonrasib also represents an important scientific milestone.

RAS proteins have long been recognized as major drivers of cancer, but researchers struggled for decades to develop drugs capable of effectively targeting them.

That challenge has been especially significant in pancreatic cancer, where RAS alterations are found in the vast majority of tumors.

Daraxonrasib is a once-daily pill that targets multiple forms of RAS, potentially making targeted treatment relevant to a much larger group of pancreatic cancer patients than previous precision therapies.

Who Could Benefit?

The clinical trial supporting the approval primarily studied patients whose cancer had progressed following first-line chemotherapy.

But the FDA label also includes patients who have not previously received systemic treatment if they are not candidates for multiagent therapy. That could be particularly important for patients who are too frail to tolerate intensive chemotherapy.

Garrido-Laguna says daraxonrasib is generally better tolerated than combination chemotherapy. He also pointed to previously presented data showing a response rate of about 48% when the drug was used alone as an initial treatment, compared with response rates generally ranging from the 20% range to about 31% with leading chemotherapy regimens.

A Starting Point, Not the Finish Line

While the approval immediately creates a new treatment option, Garrido-Laguna believes its larger impact may come from what researchers can build around it.

Daraxonrasib could provide a new foundation for combination therapies designed to further improve outcomes for pancreatic cancer patients.

“In summary, this is an unprecedented advance in the treatment of patients with metastatic pancreatic cancer,” Garrido-Laguna said. “We have never seen this magnitude of benefit in any clinical trial conducted in this disease before.”

And he sees the approval as only the beginning.

“I still want to see this as the first step to build upon with novel combinations that we will develop in the next year, with the hope that we’re going to have a much more meaningful impact in patients with this disease in the next few years,” he said.