Carlos Becerra, MD, discusses sequencing strategies, immunotherapy, and practice-changing clinical trials in the field of pancreatic cancer.
Carlos Becerra, MD
Emerging data are changing the treatment paradigm in pancreatic cancer, offering patients new options and more personalized care, according to Carlos Becerra, MD.
In an interview during the 2018 OncLive® State of the Science Summit™ on Gastrointestinal Malignancies, Becerra, medical oncologist, Texas Oncology, discussed sequencing strategies, immunotherapy, and practice-changing clinical trials in the field of pancreatic cancer.Becerra: I talked a little bit about frontline chemotherapy for patients with metastatic pancreas cancer and how best to sequence the different agents that we have available to try to improve survival in these patients.Right now, we do not have a head-to-head comparison between the different agents. Therefore, in younger patients with a robust performance status there is a trend to treat them with FOLFIRINOX.
In older patients who are not as robust, there is a tendency to treat them with gemcitabine and nab-paclitaxel (Abraxane) first. Upon disease progression, we can use the other regimen that was not used. If you start with gemcitabine and nab-paclitaxel and the patient's tumor gets worse, you can consider adding or changing to either FOLFIRINOX if the patient still has a very good performance status or a variation, such as FOLFOX. Another regimen that can be utilized is liposomal irinotecan in combination with 5-FU, which is approved for second-line chemotherapy in this particular setting.There is a subtype of patients with pancreas adenocarcinoma who might benefit from immunotherapy [approaches]. In this particular case, we are talking about antibodies directed against PD-1/PD-L1 inhibitors. [These patients] have a specific mutation in one of the mismatch-repair genes called MSI-H tumors. That is across the board, not just for pancreas cancer. [In pancreas cancer] about 5% to 7% of [patients] might have it, so it might be worthwhile to test for and consider the use of any of these agents.
A couple agents are commercially available, one of which is FDA approved for this particular indication. In addition to that, there are early indications that in the tumors that are not MSI-H, the immunotherapy drugs might have an effect in combination with other immune checkpoint inhibitors or inhibition of other pathways. It is exciting because we are starting to see that what was once considered a very sterile field of immunotherapy in this particular setting may not be the case [anymore].Yes. Right now, there are clinical trials with immune checkpoint inhibitors plus drug x or y. We have [also] entered the realm of using cellular-based therapies; chimeric antigen receptor T-[cell therapy] is an example of that. [Essentially, a patient’s T cells are modified] after the cells have been taken out. They have been enriched with a transfection of a specific number of genes. Then there is a protein that is a product of that which targets a specific antigen on the surface of the tumor. That approach has been under study at other centers with what appears to be mixed results, but it continues to be a very promising approach and one that we have to continue working on. It has worked in other types of tumors and might work in combination with immune checkpoint inhibitors [in pancreas cancer].The first take-home message is sequencing. [You have to make] sure that you are sequencing agents to get the most out of each therapy or combination. I also spoke about a couple studies that were presented at the 2018 ASCO Annual Meeting that are changing the pattern of the way we treat patients [outside of the metastatic setting. These are patients] whose tumors have been resected or patients whose tumor is potentially resectable and receive [neoadjuvant] chemotherapy and radiation therapy. I concentrated a little bit more on those 2 studies because they are relatively new. They are practice changing studies.The one study is PRODIGE 24. That particular study is looking at the use of adjuvant FOLFIRINOX versus gemcitabine in patients with resected pancreas adenocarcinoma. The second study, also a European study, looked at radiation therapy in combination with gemcitabine prior to resection versus surgery. The results are impressive enough that they're worth considering in general practice.