For decades, pancreatic cancer has been one of the deadliest cancers to fight. Now, doctors have a powerful new weapon.
The third-leading cause of cancer death in the US, pancreatic cancer has one of the lowest survival rates of any major cancer. The five-year relative survival rate is just 13% and death rates have remained largely unchanged for years.
That grim outlook could be starting to change, thanks to a first-of-its-kind treatment for patients with advanced disease.
In August, the FDA approved Rasonque (daraxonrasib), the first broad RAS-targeted therapy approved for metastatic pancreatic adenocarcinoma. Clinical trial results have showed slower disease progression, prolonged survival and delayed declines in pain and quality of life compared with chemotherapy.
But while approval marks a significant advance, this treatment isn’t a cure, and much work remains to improve outcomes and catch the disease earlier.
Here’s what to know about what new treatment means for pancreatic research, earlier-stage disease and the future of treatment.
The cancer that hides in plain sight
Pancreatic cancer can grow rapidly and be particularly difficult to detect early enough for surgery and chemotherapy — the only established potentially curative treatment — because the pancreas sits deep inside the abdomen.
By the time symptoms such as abdominal or back pain, unexplained weight loss, loss of appetite, fatigue or jaundice appear, the disease may already be advanced.
That makes it especially important to act quickly when pancreatic cancer is suspected or diagnosed.
Who faces the greatest risk
The exact cause of pancreatic cancer is unknown in most cases, but age — particularly being 65 or older — is the biggest risk factor.
Additional risk factors include smoking cigarettes, cigars or using tobacco, obesity, diabetes and exposure to pesticides and certain chemicals.
A family history or inherited gene mutation of pancreatic cancer also increases risk, although having a family history does not mean someone will necessarily develop the disease.
New symptoms can also warrant attention, particularly in older adults.
Unexplained weight loss, new abdominal or back pain or newly developed diabetes can sometimes signal a problem with the pancreas and should be evaluated by a doctor.
Inside the new cancer-fighting drug
RAS is a protein involved in signaling that tells cells to grow. When RAS is abnormally activated, those signals can remain switched on, causing cells to multiply uncontrollably.
RAS mutations are found in more than 90% of pancreatic adenocarcinomas, making the pathway an important target for treatment.
Daraxonrasib, sold under the brand name Rasonque, is an oral RAS inhibitor that blocks activated RAS signaling. Unlike treatments that target a single mutation, it is designed to inhibit multiple forms of RAS.
The Phase 3 RASolute 302 trial found that patients with previously treated metastatic pancreatic cancer who received daraxonrasib had a median overall survival of 13.2 months, compared with 6.7 months among those receiving standard chemotherapy.
Those results are a major advance because pancreatic cancer has historically had relatively few effective treatment options. However, this is not a cure. Most patients eventually develop resistance, with their tumors growing despite treatment.
That makes daraxonrasib an important beginning rather than an endpoint. The hope is that the drug will open the door to additional therapies targeting the same pathway, as well as combinations that could produce even greater benefits.
What’s next for pancreatic cancer treatment
Researchers are continuing to investigate ways to harness the immune system against pancreatic cancer, including vaccines and other forms of immunotherapy.
There have been promising studies, but immunotherapy has not yet produced the kind of breakthrough in pancreas cancer as seen with some other cancers.
The field is still looking for ways to make pancreatic tumors more vulnerable to attack.
The approval of Rasonque shows what can happen when researchers successfully target a fundamental driver of pancreatic cancer. The next challenge is determining whether that progress can be extended to earlier-stage disease, overcome treatment resistance and ultimately lead to cures.
The race for earlier detection
Early detection remains one of the biggest challenges because of its location inside the body.
People at particularly high risk may undergo regular imaging to look for early changes. For most people, however, pancreatic cancer is diagnosed after symptoms appear.
Researchers are investigating several approaches to earlier detection, including blood tests that could identify biological changes associated with cancer, as well as more sophisticated imaging and artificial intelligence that could help identify subtle abnormalities that might be difficult for the human eye to recognize.
When pancreatic cancer is detected early enough to consider surgery, patients should be evaluated by an experienced multidisciplinary team to determine whether the tumor can be safely removed.
Dr. Paul Oberstein is service chief of the Gastrointestinal Medical Oncology Program and assistant director of the Pancreatic Cancer Center at NYU Langone’s Perlmutter Cancer Center. He specializes in caring for people with gastrointestinal cancers, with a particular focus on pancreatic cancer and developing new approaches to treatment.
