For decades, pancreatic cancer has been one of the most difficult cancers to treat, with chemotherapy often offering patients limited options once the disease has spread. But new drugs targeting the RAS pathway, a key driver of pancreatic cancer growth, are beginning to change that outlook. These therapies are giving oncologists new ways to attack the disease and offering patients renewed hope.
For Raj Vaghjiani, MD, a surgical oncologist at The University of Texas Medical Branch (UTMB Health), the recent U.S. Food and Drug Administration (FDA) approval of the new drug daraxonrasib is another sign that researchers are making meaningful progress against a cancer that has long resisted treatment.
Targeting a pathway that drives cancer growth
RAS is part of a molecular signaling system that tells cells when to grow and divide. In many pancreatic cancers, mutations in the RAS pathway keep those growth signals turned on, causing cancer cells to continue multiplying.
New drugs that target this pathway give physicians a way to interrupt those signals and attack cancer cells more precisely.
“Researchers in a Phase 3 clinical trial published in the New England Journal of Medicine found that patients with metastatic pancreatic cancer who received a new drug called daraxonrasib had nearly doubled the median survival of those who received standard chemotherapy, which is extraordinarily good news,” Vaghjiani said.
Daraxonrasib has since moved from the investigational stage into clinical use. On Aug. 26, the FDA approved the drug for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent therapy. It is the first FDA-approved drug in a new class of RAS-targeted therapies.
Daraxonrasib is a once-daily pill that targets RAS proteins, which act as growth signals in cancer cells. In the Phase 3 trial, patients treated with the drug had a median overall survival of 13.2 months, compared with 6.7 months for patients who received standard chemotherapy. The drug also delayed disease progression and produced tumor responses in more patients.
“This success has spurred more research, and we are finding ways to use this drug to treat pancreatic cancer earlier,” Vaghjiani said. “It’s exciting to have this new option for patients who, until now, have largely been treated with chemotherapy. It is helping extend survival and creating new opportunities to improve care.”
Although it is difficult to predict which emerging therapy will ultimately have the greatest impact, Vaghjiani said it is encouraging to see new approaches beyond traditional chemotherapy being explored.
The approval of daraxonrasib does not mean RAS-targeted treatments have solved pancreatic cancer. The drug is currently approved for patients with metastatic disease who have already received treatment, and researchers are continuing to study whether RAS-targeted therapies can be used earlier in the disease.
Personalized vaccines target recurrence
Another promising area of research involves personalized mRNA vaccines, which are being studied as a way to reduce the risk of pancreatic cancer returning after surgery.
“Now, individualized mRNA vaccines are being tested for pancreatic cancer, and we are seeing encouraging early results,” Vaghjiani said. “It’s too early to know which approach will be most effective, but many are showing promise, and that’s a good sign. We are no longer limited to treating this disease the way we always have.”
With pancreatic cancer, preventing recurrence is critical. The vaccine Vaghjiani described would be tailored to the unique characteristics of a patient’s tumor. The tumor would have been surgically removed before the vaccine was administered.
The word “vaccine” may sound like a preventive treatment, but in this case, the vaccine would be administered after cancer has already developed. Using information from a patient’s tumor, researchers would create a personalized vaccine designed to train the immune system to recognize and attack cancer cells that may remain in the body and could cause the disease to return.
These approaches remain experimental, and researchers must establish their safety and effectiveness through clinical trials before they become widely available.
“We aren’t there yet,” Vaghjiani said. “Cancer treatments often begin as experimental therapies and must go through clinical trials to evaluate their safety and effectiveness.”
Moving treatment earlier
New therapies are often tested first in patients with advanced disease. When outcomes improve, researchers can begin studying whether those treatments might be effective earlier in the course of the disease.
“We are still in the early phases of discovery and investigation,” Vaghjiani said. “The ultimate goal is to use these therapies before surgery and, one day, make surgery unnecessary for some patients.”
That goal remains part of the research into RAS-targeted therapies. Although daraxonrasib is now approved for certain patients with metastatic pancreatic cancer, researchers are studying whether drugs that target the RAS pathway could eventually play a role earlier in treatment, including before surgery.
A more hopeful treatment landscape
For patients with advanced pancreatic cancer, the emergence of new treatment strategies represents an important shift.
“It’s no longer chemo or nothing,” Vaghjiani said. “Treatment is becoming a very different conversation, with new therapies and new drugs that can help patients live longer after a devastating diagnosis.”
Vaghjiani said patients with pancreatic cancer should be evaluated promptly and consider seeking care at a specialty center, particularly because pancreatic cancer is relatively uncommon and treatment can be complex.
The recent FDA approval marks an important change in the treatment landscape. Other RAS-targeted drugs remain under investigation, and researchers are studying how these therapies might be used in combination with other treatments and earlier in the course of pancreatic cancer.
Looking five to 10 years ahead, Vaghjiani hopes these therapies will be available earlier in treatment.
“No matter what, there’s always a risk of cancer coming back,” he said. “But new therapies are helping us reduce that risk. The ability to delay recurrence longer and longer is very exciting.”