Expert Highlights Latest Developments in Early and Locally Advanced Pancreatic Cancer

Diane Simeone, MD

In early and locally advanced pancreatic cancer, treatment strategies vary depending on a patient’s resectable status, and even then, it can be challenging to determine whether neoadjuvant or adjuvant therapy should be given, said Diane Simeone, MD.

“When we think about who should receive neoadjuvant therapy and has locally confined pancreatic cancer, we need to look at the resectable, borderline, and locally advanced and resectable categories,” explained Simeone, director of the Pancreatic Cancer Center at NYU Langone Health’s Perlmutter Cancer Center.

Additionally, there continues to be a need for more widespread adoption of genetic testing in pancreatic cancer, said Simeone, adding that such tests can help identify individuals at higher risk for the disease.

In an interview during the 2020 OncLive^® State of the Science Summit™ on Gastrointestinal Malignancies, Simeone discussed recent data on neoadjuvant and adjuvant therapy for patients with locally advanced or resectable pancreatic cancer, and questions surrounding germline testing for earlier identification of this disease.

OncLive: Which patients with pancreatic cancer should receive neoadjuvant therapy?

Simeone: When we think about who should receive neoadjuvant therapy and has locally confined pancreatic cancer, we need to look at the resectable, borderline, and locally advanced and resectable categories.

For the resectable category, it is not in the guidelines that patients should receive neoadjuvant therapy. The standard of care is for patients to receive a high-quality, thin-slice CT scan for proper staging. If a tumor is deemed resectable, then a patient can be offered a surgical resection. With that being said, surgery alone is not the only tool we use to treat those patients. The standard of care today says that following recovery from surgery, which is typically 4 to 6 weeks, [adjuvant] chemotherapy is recommended and is used to help minimize the risk of disease recurrence.

The other factor is that, even with a technically perfect operation and giving the right adjuvant chemotherapy, there is still a risk of disease recurrence. Patients who have bigger tumors are treated with neoadjuvant chemotherapy. In the future, we will see some clinical trials [having an impact on] giving more neoadjuvant therapy in resectable patients.

Borderline and locally advanced patients are given neoadjuvant therapy. Neoadjuvant therapy will often start with a combination chemotherapy of either FOLFIRINOX or gemcitabine/nab-paclitaxel (Abraxane). If you compare the 2 regimens, we tend to give more patients

FOLFIRINOX; sometimes radiation is added after chemotherapy. However, there are still equivocal data about that; it is usually several months of combination chemotherapy, reimaging by a team of experts, and if appropriate, surgical resection.

We also might give chemotherapy after surgery, but we do not have good data to guide us on this. There is a critical missing piece of data that we need to acquire in the clinical trial setting so we can be smarter about how we treat patients.

What practice-changing data have been presented in this setting?

There have been some big studies in the adjuvant setting. The Unicancer GI Prodige 24/CCTG PA.6 study compared FOLFIRINOX with gemcitabine after surgery. Patients who were treated with FOLFIRINOX fared much better with a [median overall] survival (OS) of 54.4 months compared with a median OS of 34.8 months with gemcitabine.

Along the same lines, in terms of comparison, was a study on gemcitabine plus nab-paclitaxel compared with gemcitabine alone in the adjuvant setting. Everyone was surprised because a [survival] difference was not seen. However, the data are not fully mature, and it might be that as the data mature, there may be a small difference in OS. We need to wait to see.

What screening methods are in the pipeline for earlier identification of pancreatic cancer?

All patients with pancreatic cancer should get germline testing. Germline testing helps us identify family members who might be at risk and help get them the screening they need. We want to make sure that people know whether they have family members or parents with pancreatic cancer, or if they have or a family history of pancreatic cancer—especially if it is associated with other cancer types. These patients should seek [out a genetic counselor] about whether or not they should get germline testing and screening done.

For those identified as high-risk for pancreatic cancer, we do recommend annual screening, a pancreatic MRI or magnetic resonance cholangiopancreatography, alternating with an endoscopic ultrasound. We recommend that happens in the setting of a high-risk clinic, where there is a genetic counselor and a team of physicians involved.

Could PARP inhibitors be approved in earlier settings of pancreatic cancer?

PARP inhibitors are beneficial in the doubling of progression-free survival for [select] patients with pancreatic cancer. [The questions that arise are], “Might we get a further advantage by combining a PARP inhibitor with another agent?” and “In the nonmetastatic setting, what do we do if we operate on someone and they have a germline BRCA mutation? Should that change their adjuvant therapy?”

You could envision a day that PARP inhibitors are used in a preventative setting for patients who have germline BRCA mutations, but that is still several years off.