Pancreatic Cancer Moon Shot sharpens pre-surgical treatment
Clayton R. Boldt, Ph.D.
Neoadjuvant therapy is treatment, such as chemotherapy or radiation, given before a patient has surgery. This approach is used in many cancer types to treat microscopic disease that has spread to other organs (micro-metastases) or shrink the primary tumor before proceeding with surgical removal. However, this approach has not been widely adopted in the community when treating patients with pancreatic cancer.
Over the past two decades, MD Anderson clinicians pioneered the use of neoadjuvant therapy for treating pancreatic cancer, and many of them now are working as part of the Pancreatic Cancer Moon Shot™ team to improve outcomes for patients. The effort is part of MD Anderson’s Moon Shots Program™, a collaborative effort to develop scientific discoveries into clinical advances that save patient’s lives.
He spoke with Cancer Frontline to share more about the Moon Shot’s goal to offer more patients access to a clinical trial to improve their outcomes.
Q: Can you describe MD Anderson’s role in developing neoadjuvant therapy approaches for pancreatic cancer and describe the value of this approach?
A: Neoadjuvant therapy is a therapy given before doing surgery for pancreatic cancer. Even though the cancer might appear to be confined to the pancreas, more often than not it’s unfortunately already metastasized. It’s a very aggressive disease and there may already be microscopic metastases that we can’t detect on CT or MRI scans in the liver or elsewhere.
Also, surgeries for pancreatic cancer are generally highly morbid. Most of the time, we’re required to do a procedure called a Whipple surgery, which can have life-changing effects for the patient. And if a patient has metastatic disease at the time of surgery, we aren’t helping the patient by doing such a surgery.
The idea with neoadjuvant therapy is to give some chemotherapy — systemic therapy that goes throughout the body system — to try to kill off those individual cells that we suspect are there. Then, we’re able to identify patients who respond well to treatment, and can properly treat the ones we think have a cancer confined to the pancreas and should benefit from surgery.
MD Anderson surgeons, medical oncologists and radiation oncologists were among the first to push this concept forward in pancreatic cancer. That’s been our approach to treating the disease for about two decades, and it seems that more and more practices out there are beginning to adopt this concept. There are clinical trials now also showing promise with the neoadjuvant approach.
Q: Your work in the Moon Shot is focused on developing a platform for adaptive clinical trials to make these trials accessible to more patients. Can you describe how this adaptive platform works?
A: Most experimental trials for pancreatic cancer are done for patients with late-stage, metastatic disease as opposed to the early stage, pre-operative space. There just aren’t as many patients diagnosed with earlier-stage disease, so it’s hard to do conduct those trials.
This platform trial is a Phase II randomized study that allows us to gain some efficiencies over the typical trial design. Patients on the trial will be randomized to either a control arm, which is standard neoadjuvant therapy followed by surgery, or an experimental arm, which is standard neoadjuvant therapy plus the treatment we are investigating.
On the platform trial, you can add experimental arms over time while maintaining the same control arm. This way, you’ll always have the comparator of the control arm, without having to replicate the control arm each time you test a new experimental therapy. In a traditional approach, five experimental therapies would require five distinct control arms. With the platform trial, we have a single control group that can be expanded and adapted over time as needed, or as standard of care changes.
Also, because we’re removing the tumors at the time of surgery, we’re able to analyze the pathological response rate at that time. This is the primary endpoint of our trial, rather than progression-free or overall survival. For those endpoints, you must follow the patient until the cancer comes back, which requires much more time.
By looking at the tumor under the microscope and gauging how the cancer cells have died off after neoadjuvant therapy, we get an early readout of outcome to allow us to accelerate research and translate our findings to patients faster. We’ve shown that pathological response rate is a good predictor of overall survival in pancreatic cancer, so that’s why we chose this as our endpoint.
Q: How does this approach benefit the patients?
A: First and foremost, we want to try to offer things that are exciting and promising for our patients. Otherwise there's really no reason to try to pursue something like this.
The idea with this neoadjuvant platform trial is to try new experimental therapies while also studying tissue from patient tumors to understand how those therapies are working and how patients are responding. That provides us with a unique opportunity. With metastatic patients, usually all you can do is a CT scan or biopsy of metastatic sites to study the tumor cells.
With neoadjuvant therapy, your intent is to be able to take that patient to surgery, remove the entire tumor from the pancreas and then analyze it. This allows us to study biomarkers, protein levels, gene expression, mutations and a number of different things happening at the microscopic scale to understand how the drug is actually working.
Our hope is that by doing this, we’ll be able to gain some insight that we can apply to the vast majority of patients with metastatic cancer. For example, we may find biomarker signatures that help us eventually select a particular therapy for a particular patient who will most benefit from that drug.
Q: Are there any aspects of the project you’re particularly excited about?
A: We just recently announced an alliance with a pharmaceutical company called Nanobiotix. They have a nanoparticle that is injected directly into the tumor to help enhance the radiation effects within the area the nanoparticle resides. It’s a radiation sensitizer to help kill the tumor cells.
They’ve already tested this approach in patients with sarcoma, with patients receiving either radiation alone or radiation plus the nanoparticle. They found that the pathological complete response rate was doubled with injection of the nanoparticle into the tumor compared to radiation alone.
I’m excited to see how we can bring this drug and other new therapeutic options forward for our patients.
Q: How has your work been enabled by the Moon Shots Program and its infrastructure?
A: It’s been a tremendous help for me and my team. I think it was a visionary endeavor, honestly, to set the whole institution forward with the goal of ending cancer, especially highly aggressive forms like pancreatic cancer. It’s really helped to organize us as a team. We have clinicians and researchers from many different disciplines working together, with very specific objectives to try and combat the disease.
Eugene Koay, M.D., Ph.D., assistant professor of Radiation Oncology,
explains how the adaptive clinical trial platform will allow the team
“to offer things that are exciting and promising for our patients.”