ctDNA Testing in Pancreatic Cancer

Gregory P. Botta, MD, PhD: At this point, it’s very early to know the possible clinical outcome data that we can get from ctDNA [circulating tumor DNA] in pancreatic cancer. What ctDNA in pancreatic cancer would help us understand is if there’s any chance of a patient’s recurrence from their pancreatic cancer after surgery or after adjuvant therapy.

Ultimately, ctDNA is a very early marker in pancreatic cancer. We use it to help us provide actionable mutation data, both in a tumor-naive approach as well as a tumor-informed approach. However, it’s a needle in a haystack approach. There are very limited targetable mutations in pancreas cancer. But when we come across those needle in a haystack mutations, they make a difference for our patients. Immunotherapy may be beneficial in things like IDH1 mutations, BRAF-driven pancreas cancer, or possibly even KRAS wild-type pancreatic cancer. When we do circulating tumor DNA analysis, that means a lot for those patients in whom it comes back positive.

In terms of molecular residual disease, pancreatic cancer is a very aggressive malignancy. The recommendation of all oncologists is that patients usually receive either neoadjuvant or adjuvant therapy, regardless of the staging. We’re wondering if ctDNA can help substratify a group of patients and help us determine whether they may not need adjuvant therapy or neoadjuvant therapy prior to resection. The theory is that given an aggressive malignancy, such as pancreatic cancer, that likely won’t happen. We’re trying to substratify whether our therapies are making a difference.

There are other studies that are evaluating that as well, whether you should switch a patient from gemcitabine/Abraxane to a FOLFIRINOX [leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, oxaliplatin] or oxaliplatin-based regimen, and whether the surgical resection was successful enough that the patient became molecular residual disease negative. If the patient goes to negativity but later becomes positive, are we able to treat earlier and change that patient’s outcome, or does it not matter? In many cases, ctDNA analysis is able to determine that there’s recurrence prior to radiographic recurrence. If that’s the case, are we able to head off a patient’s tumor burden earlier by getting them on therapy, or is it just lead time bias? These are questions that need to be answered.

Transcript edited for clarity.