A new drug called daraxonrasib nearly doubled survival time for patients enrolled in a phase-3 clinical trial. That’s a big deal, because treatment options for pancreatic cancer are limited and survival rates at 5 years are very low.
In 2002, my grandmother was diagnosed with pancreatic cancer. Six months later she was admitted to hospice, and less than a year after her diagnosis, she passed away. I can still remember how alarmingly fast the disease took her. It felt like one day she was her usual energetic self, and the next she was fading away before our eyes.
More than 20 years later, treatment options that slow progression and extend life remain far too limited for many people diagnosed with pancreatic cancer. Regardless of stage, only 13% of people diagnosed with pancreatic cancer are still alive after 5 years [archived link]. Despite the fact that pancreatic cancer only accounts for about 3% of all annual cancer diagnoses, it is the third leading cause of cancer deaths in the U.S., after lung and colorectal cancers [archived link].
What is pancreatic cancer?
There are two main types of pancreatic cancer: exocrine and endocrine. Pancreatic exocrine cancer arises from cells that produce digestive juices and includes the most common type of pancreatic cancer (pancreatic ductal adenocarcinoma, or PDAC). Pancreatic endocrine cancer occurs when tumors form in pancreatic cells that produce hormones. It is much rarer than PDAC and makes up less than 5% of all diagnoses. Unfortunately, the PDAC is also one of the most aggressive types of cancer that has ever been discovered. Pancreatic cancer cells are nested within tough scar tissue, and the genetic changes, or mutations, that cause the cancer also result in changes to the pancreas that further support its survival and growth. Compared with other gastrointestinal cancers, pancreatic cancer is often harder to treat with traditional chemotherapy because of these unique features.
Why is pancreatic cancer so difficult to diagnose and treat?
Source: PDQ Cancer Information Summaries
Part of the difficulty of diagnosing and treating pancreatic cancer is simply the location of the pancreas. It is a small organ that sits deep in the abdomen just below the liver and behind the stomach. Because of this, it is not possible for a clinician to examine from the outside of the body.
Even more problematic is the fact that early symptoms of pancreatic cancer are either mild and non-specific (meaning that they can be caused by a wide range of other health problems), or absent altogether. There are also no reliable routine early screening tools available. Pancreatic cancer survival rates are much better when a diagnosis is made early when surgery is still possible (discussed below), but because it is so difficult to detect, it is usually caught later when treatments are no longer as effective.
What are the risk factors for pancreatic cancer?
Pancreatic cancer has many of the same risk factors as other more common cancers. It is usually diagnosed in older patients, with average age at diagnosis around 70 years old. Other common risk factors include tobacco use, having excess body weight, type 2 diabetes, chronic pancreatitis, and heavy exposure to chemicals used in dry cleaning and metal-working. There are also some genetic risk factors for pancreatic cancer. For example, genes that cause hereditary breast cancer (BRCA1/BRCA2/PALB2) also raise the risk for pancreatic cancer. However, only 1 in 10 people with pancreatic cancerhave an identifiable inherited risk factor. It is also worth noting that cancer, including pancreatic cancer, disproportionately affects some groups more than others due to health disparities.
What treatments are available?
The usual cancer treatments, such as surgery, chemotherapy, and radiation, are currently used to treat pancreatic cancer. People treated with surgery tend to have the best chance of survival because surgery is only possible if the cancer is caught early, before it has spread. Surgery is also the only treatment that can cure pancreatic cancer. There are few second-line options to treat pancreatic cancer besides additional chemotherapy. There are some immunotherapy options and newer targeted therapies, but only a small percentage of patients qualify for them. There are ongoing clinical trials to develop more immunotherapies.
What is daraxonrasib and what makes it different?
Daraxonrasib is a type of drug known as a targeted RAS inhibitor [archived link]. Some cancers make a broken version of a protein called RAS. In healthy cells, RAS acts like a light switch. It briefly turns on a “grow and divide” signal, then turns it off. In cancer cells, RAS can get stuck in the “on” position, causing uncontrolled growth. Daraxonrasib interferes with that stuck switch, preventing the cancer cells from getting the signal to keep growing.
Daraxonrasib is still undergoing clinical trials, but early results have been promising[archived link] and it is expected to become the new second-line standard of care[archived link]. Importantly, daraxonrasib can be effective for treating PDAC, the most common type of pancreatic cancer. More than 90% of metastatic PDACs are caused by a mutation in the KRAS gene, called a RAS G12 variant, that results in an overactive KRAS protein. Previously available RAS inhibitors are specific to one of the altered versions of the protein, but daraxonrasib is a new kind of RAS inhibitor called a RAS(ON) multi-selective inhibitor. It can turn off the KRAS protein to stop cancer growth whether there is a KRAS variant or not, and regardless of which variant it is. Daraxonrasib is taken as a daily pill and usually has fewer side effects compared to traditional chemotherapy and radiation.
All patients who received daraxonrasib in the phase-3 clinical trial had already received chemotherapy. Participants were randomized to receive either daraxonrasib or additional chemotherapy. The average survival time was doubled in the daraxonrasib group, from 6.7 months to 13.2 months [archived link]. That may not seem like a lot, but the patients in this trial had advanced cancer that had failed to respond to other treatments. This is a very promising treatment direction and may lead to further discoveries that will lead to better outcomes for people diagnosed with pancreatic cancer. More studies to determine if daraxonrasib can be used as a first-line treatment are currently underway.
Bottom Line
Pancreatic cancer is one of the most serious cancer diagnoses a person can receive because it is usually caught late and is difficult to treat. While the outlook has remained stubbornly poor, new advances in immunotherapy (including personalized mRNA vaccines), and RAS inhibitors may finally give people and families affected by pancreatic cancer powerful tools that will extend and improve their lifespans.
Stay well, stay safe.
Love,
Those Nerdy Girls
Resources and further reading:
Memorial Sloan Kettering Cancer Center – What to Know about Pancreatic Cancer
UC Health Today – A new pancreatic cancer drug is changing survival rates for one of the deadliest cancers [archived link]
Hirshberg Foundation – FDA Expands Access to Daraxonrasib: What Patients Need to Know [archived link]
NEJM – Daraxonrasib in Previously Treated Advanced RAS-Mutated Pancreatic Cancer
Cancer Causes & Control – Trends in pancreatic cancer mortality in the United States 1999–2020: a CDC database population-based study
PanCan – Resources for Caregivers
National Comprehensive Cancer Network – Pancreatic Cancer Guidelines for Patients
