Colin Weekes, MD, PhD
Neoadjuvant therapy has become increasingly plausible for patients with advanced pancreatic cancer, as the quantity and quality of approved therapies continue to increase, according to Colin Weekes, MD, PhD.
Several studies are currently assessing neoadjuvant treatment with nab-paclitaxel (Abraxane) plus gemcitabine for patients with pancreatic cancer. Additionally, studies are looking at this combination along with other novel agents, such as FG- 3019, a monoclonal antibody that binds to connective tissue growth factor. Outside of novel agents, chemoradiation has also played a traditional role for borderline resectable disease.OncLive
interviewed Weekes, associate professor, Department of Medicine and Medical Oncology, University of Colorado, to gain further insight into the current state and future directions for neoadjuvant therapy for pancreatic cancer.
OncLive: What is the current state for neoadjuvant regimens in pancreatic cancer?
: The role of neoadjuvant chemotherapy and radiation for pancreatic cancer is undergoing a metamorphosis.
Over the last several years, we’ve found it feasible to give combination chemotherapy to patients with metastatic disease. What we’ve seen with that is an increase in the survival of patients associated with the combination chemotherapy, as well as an improvement in response rates. So the tumor shrinks as we give it chemotherapy.
This is now being applied in earlier stage disease where the cancer is still potentially resectable, or borderline resectable. There are a lot of different chemotherapy regimens being used in that situation, such as FOLFIRINOX or a combination of gemcitabine and nab-paclitaxel. The other component that has evolved over this course of time as well is the types of radiation therapy that we can give.
Historically, radiation therapy for pancreas cancer has been a combination of chemotherapy and radiation over usually a 5-week course of therapy. Now we can give more conformal radiation, which doesn’t necessarily require us to give additional chemotherapy. This means a shorter overall time of radiation and higher individual doses. The nice thing about this is that if it’s administered well, there is minimal toxicity.
How are these advances being applied to borderline resectable disease?
Thinking about the issue in terms of getting a patient from neoadjuvant therapy to surgery, one of the critical issues in being able to accomplish that is toxicities associated with the therapy. By giving more effective chemotherapy and minimizing radiation-induced toxicity, as well as chemotherapy-induced toxicity, the odds of getting a patient to surgery, which is the only curable method that we have for pancreatic cancer, is much greater.
So now we are trying to give this effective therapy, improve the number of patients who actually get surgery, and improve the survival of those patients who undergo surgery for this disease. Right now, there hasn’t been a definition of what the appropriate chemotherapy is, what the appropriate lengths of time to give the chemotherapy, and if radiation is really optimal in this situation. If radiation is optimal, then is it traditional chemoradiation or is it these newer techniques which are shorter course, higher-dose radiations. Those are the principles that are currently surrounding neoadjuvant therapy. If all of that is successful, then the next step would be to add biologic therapies and immunotherapies in this setting.
What potential do you think immunotherapy could have in pancreatic cancer?
What we are finding out is that you can modulate the pancreas microenvironment. If you look at the mass of a pancreas tumor, what you’ll see under a microscope is that there are a lot of support cells, and support proteinaceous material called the stroma or desmoplastic reaction. That stroma also has immune cells, and so that is the majority of the tumor. The cancer cells are actually the minor component of that tumor.
What’s becoming increasingly realized is that you have to treat that stroma component as well as that cancer cell. Immunotherapy is one way to approach that, and it may be that giving certain kinds of chemotherapy or biologic therapies can actually manipulate the immune system such that you can turn the immune system against the cancer. It may be that giving chemotherapy may also prime the immune system to work against the cancer.
Those are questions that are being evaluated. There are no known answers. These immunotherapies might also depend on the type of molecule that you’re using as your therapy. This means there may be a difference between the abilities of bulky antibodies versus small molecule inhibitors to get to the tumor cell, or get to the target, to affect change from a biologic standpoint.