The Food and Drug Administration in August approved Rasonque (daraxonrasib), the first broad RAS-targeted therapy cleared for metastatic pancreatic adenocarcinoma, offering a new option for a disease that has defied major treatment advances for decades.
Pancreatic cancer is the third-leading cause of cancer death in the United States. Its five-year relative survival rate stands at just 13%, and death rates have changed little over the years. Doctors say the new drug does not change that broader picture overnight, but it represents the most significant single advance in years for patients with advanced disease.
In the Phase 3 RASolute 302 trial, patients with previously treated metastatic pancreatic cancer who took daraxonrasib had a median overall survival of 13.2 months, compared with 6.7 months for those on standard chemotherapy. The drug also showed slower disease progression and delayed declines in pain and quality of life relative to chemotherapy.
Why RAS matters
RAS is a protein that signals cells to grow. When RAS mutates and becomes abnormally activated, that growth signal can get stuck in the “on” position, driving uncontrolled cell division. RAS mutations appear in more than 90% of pancreatic adenocarcinomas, making the pathway a long-sought target for drug developers.
Daraxonrasib, taken orally, blocks activated RAS signaling. Unlike earlier drugs that targeted only a single RAS mutation, it is designed to inhibit multiple forms of the protein, a distinction researchers say broadens its potential use.
Doctors caution the drug is not a cure. Most patients eventually develop resistance, and their tumors begin growing again despite treatment. Researchers view the approval as an opening for additional RAS-pathway drugs and combination therapies that could extend benefits further, rather than a final answer.
A disease that’s hard to catch early
Pancreatic cancer is notoriously difficult to detect early because the pancreas sits deep in the abdomen. Surgery combined with chemotherapy remains the only established potentially curative treatment, but by the time symptoms such as abdominal or back pain, unexplained weight loss, loss of appetite, fatigue or jaundice appear, the disease has often already advanced.
Age is the single biggest risk factor, particularly for people 65 and older. Other risk factors include smoking or tobacco use, obesity, diabetes, exposure to certain pesticides and chemicals, and a family history or inherited gene mutation linked to the disease. Having a family history does not guarantee someone will develop pancreatic cancer, but doctors say new or unexplained symptoms — weight loss, abdominal or back pain, or newly diagnosed diabetes — warrant a prompt medical evaluation, especially in older adults.
Researchers are also pursuing immunotherapy approaches, including vaccines, to recruit the immune system against pancreatic tumors. Those efforts have produced some promising results but have not yet delivered the kind of breakthrough seen in other cancers, and scientists are still searching for ways to make pancreatic tumors more susceptible to immune attack.
Looking ahead
For now, early detection remains one of the field’s biggest obstacles given the pancreas’s location deep inside the body. People at high risk may undergo regular imaging to watch for early changes, but most patients are still diagnosed only after symptoms emerge. Researchers are developing blood tests to detect biological markers of the disease, along with advanced imaging and artificial-intelligence tools meant to spot subtle abnormalities that could be missed by the human eye.
Patients whose pancreatic cancer is caught early enough for possible surgery should be evaluated by an experienced multidisciplinary team to determine whether the tumor can be safely removed, doctors say.
Dr. Paul Oberstein, service chief of the Gastrointestinal Medical Oncology Program and assistant director of the Pancreatic Cancer Center at NYU Langone’s Perlmutter Cancer Center, specializes in treating gastrointestinal cancers, with a focus on pancreatic cancer and developing new treatment approaches.
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