Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. About 90% of people with pancreatic cancer have this type, which starts in the lining of the channels (ducts) in your pancreas. When PDAC is metastatic (mPDAC), it means the cancer has spread beyond your pancreas to other parts of your body.
It's common to get a PDAC diagnosis at the metastatic stage, because symptoms may not happen until cancer cells have spread to your liver, lungs, abdominal (belly) cavity, or bones. Because with mPDAC the cancer has spread to distant body parts, treatment focuses on keeping your cancer from getting worse, not curing it.
"It's still very treatable, and we hope there are going to be very new options in the very near future, but in most cases when it is metastatic, the goal of treatment is to control the disease for as long as possible," says Neeha Zaidi, MD, a medical oncologist at Johns Hopkins Medicine.
Although chemotherapy is still the standard for treating mPDAC, pancreatic cancers with certain genetic mutations can be treated with targeted therapies. Clinical trials are ongoing to develop new targeted therapies that show promise for personalized treatment decisions and helping you live longer with a better quality of life.
Current mPDAC Treatments
Chemotherapy is the first-line treatment doctors choose for most people with mPDAC. Immunotherapy or targeted therapy may be given if the cancer cells have certain genetic changes. You may have other treatments such as radiation or surgery alongside chemotherapy, but only if they can help relieve pain or other symptoms of the cancer.
For example, your tumor may be blocking your bile duct, a tube that digestive fluids flow through. This can cause pain and digestive problems. Surgery can unblock your bile duct to relieve these symptoms.
Radiation may also help if you have a limited number of cancer sites, or if your tumor is pressing on nearby organs and causing pain, but it's rarely the main form of treatment for mPDAC.
Chemotherapy is the most effective treatment for mPDAC. Chemotherapy drugs attack fast-dividing cells. You get these medicines as an infusion through an IV in your vein.
"It's a systemic treatment, meaning it gets into your body and attacks all the sites of cancer," says Zaidi.
Chemotherapy works best when you take more than one chemotherapy drug at the same time. The chemotherapy combinations doctors choose most often for mPDAC are:
- FOLFIRINOX. This is a combination of four drugs: 5-fluorouracil (5-FU), leucovorin, irinotecan, and oxaliplatin. Your doctor may choose this combination if you're healthy enough to have a more aggressive approach to treatment.
- Gemcitabine plus nab-paclitaxel (GnP). This combination of two chemotherapy drugs is sometimes easier to tolerate.
Your doctor will monitor you to see whether your cancer is responding using CT scans, Zaidi says.
"We also look at tests, like a CA-19-9, which is something that we can measure in the blood," she says. This helps us get an idea fairly early on whether you're responding or not. And if you're not, we usually switch to the other type of chemotherapy."
Typically, the way doctors choose which chemotherapy to start with is based on things such as how active you are in your daily life, other health conditions you have, and your liver and kidney function. But other ways to choose the most effective chemotherapy are in the works, Zaidi says.
"There are now more studies looking at whether there's certain biomarkers that might predict one patient responding better to one versus another, but that's still in a research phase as opposed to something that we really use clinically on a day-to-day basis," says Zaidi.
Chemotherapy side effects
Although they can vary from person to person, some chemotherapy side effects are especially common in mPDAC treatment.
They include:
- Fatigue
- Nausea and vomiting
- Diarrhea
- Low blood counts
- Increased infection risk
- Numbness and tingling in the hands and feet (neuropathy)
- Hair loss
There are ways to manage many of these side effects, but if you continue to have problems, your doctor can explore options like changing your dosage, Zaidi says.
Treatment Advances on the Horizon
Treatments for mPDAC may be changing drastically in the near future. Clinical trials of medicines that can target and kill cancer cells with a common mutation are showing promise. Some of the tools doctors have started to use to better understand your mPDAC are genetic and biomarker testing.
"We now take a tissue sample from each person to understand the genetic makeup of their cancer," Zaidi says.
This testing, often called next-generation sequencing (NGS), looks for mutations or genetic alterations that may help guide treatment decisions. One of the most important mutations in pancreatic cancer involves the KRAS gene.
"KRAS is altered or mutated in about 90-plus percent of people with mPDAC," Zaidi says.
This information helps researchers understand more about what drives cancer growth, which can also help tailor treatments for it. Some of these mutations may open the door to targeted therapies or clinical trials.
Doctors can also do germline testing, which looks for certain inherited mutations that may run in families. About 10% of pancreatic cancers are linked to inherited genetic changes.
"These tests look at the genes that may have been passed down that may put you at risk," Zaidi says. "And that's important not only for family members to know, because there are now early screening tests, but also because there are targeted therapies available for certain germline mutations."
Targeted therapy
Targeted therapies are drugs that attack specific mutations or pathways inside cancer cells. Unlike chemotherapy, which affects rapidly dividing cells throughout the body, targeted therapies focus on molecular changes on cells to "see" and attack them specifically.
The FDA has already approved some targeted therapies for small groups of people with pancreatic cancer, particularly people with BRCA mutations and certain other gene changes. But researchers are especially excited about KRAS inhibitors, Zaidi says.
"These have shown really promising clinical efficacy," she says.
Many KRAS inhibitors are pills instead of IV chemotherapy. Researchers are studying them in clinical trials for several KRAS mutations. Early studies suggest these therapies may help a large proportion of people with pancreatic cancer because KRAS mutations are so common, Zaidi says.
The FDA has approved daraxonrasib (Rasonque) to treat pancreatic cancer that has spread to other parts of the body. Daraxonrasib blocks RAS proteins, which fuel cancer cell growth. By shutting down these proteins, daraxonrasib can slow cancer cell growth and may cause cancer cells to die.
Targeted therapies can still cause side effects, though they are often different from chemotherapy side effects. "With the KRAS inhibitors, you tend to get more of a skin rash," Zaidi says. The RAS inhibitor can cause rash, diarrhea, nausea, vomiting and abdominal pain. "Generally speaking, the targeted therapies are pretty well tolerated."
Immunotherapy and vaccines
Immunotherapy with checkpoint inhibitors can be given to treat people who have MSI-high tumors (cancers with a high number of DNA mutations caused by a failure in the cell's "mismatch repair" or MMR system). Checkpoint inhibitors modify the immune system to help it find and destroy cancer cells.
There are no FDA-approved vaccines for pancreatic cancer. Clinical trials are currently being performed to test therapeutic vaccines.
Questions to Ask Your Doctor
Several questions are especially important to ask early in your treatment so that you understand your options and goals of treatment. These include:
- What stage is my cancer?
- Should I get next-generation sequencing?
- Should I have germline genetic testing?
- Am I eligible for targeted therapy?
- Are there clinical trials that fit my cancer?
- Which chemotherapy do you recommend and why?
- What side effects should I expect?
- How will we know if treatment is working?
Getting a second opinion if you feel like you could benefit from more information, especially if you have access to a tertiary care center or specialized cancer center, is encouraged, Zaidi says. "Often there's a high volume of pancreatic cancer being seen because they may have access to more trials at these centers."
"This allows us as oncologists to work with one another to figure out what the best treatment paradigm is," she says.
Show Sources
Photo Credit: iStock/Getty Images
SOURCES:
Neeha Zaidi, MD, medical oncologist, Johns Hopkins Medicine.
Johns Hopkins Medicine: "Pancreatic Cancer Types."
The Oncologist: "Clinical outcomes and molecular characteristics of lung-only and liver-only metastatic pancreatic cancer: results from a real-world evidence database."
MD Anderson Cancer Center: "Pancreatic Cancer Treatment."
American Cancer Society: "Radiation Therapy for Pancreatic Cancer," "Chemotherapy for Pancreatic Cancer."
Pancreatic Cancer UK: "Side effects of chemotherapy."
Lustgarten Pancreatic Cancer Research: "From Undruggable to Unstoppable: The State of KRAS Drug Development in Pancreatic Cancer."
Journal of Clinical Oncology: "Germline screening rates and patterns for patients with pancreatic cancer at an academic medical center."
eBioMedicine: "A comprehensive analysis of candidate genes in familial pancreatic cancer families reveals a high frequency of potentially pathogenic germline variants."
Facing Our Risk of Cancer Empowered (FORCE): "Treatment for Pancreatic Cancer."
ClinicalTrials.gov: "Mutant KRAS-Targeted Long Peptide Vaccine for Patients at High Risk of Developing Pancreatic Cancer."
eCancer: "Research reveals how pancreatic cancer blocks immunotherapy."
FDA: Label, "(daraxonrasib) Rasonque."
