expert roundtables

Optimism With Recent Advances in First- and Second-Line Treatment Options in Metastatic Pancreatic Cancer

by Thomas A. Abrams, MD, Alok Khorana, MD, Michael Morse, MD, MHS, FACP

Overview

The incidence of metastatic pancreatic cancer has increased over the past several decades, and it now ranks as the fourth leading cause of cancer death in the United States. Despite the high mortality rate, there is optimism surrounding improved outcomes with newly developed treatment regimens. Our featured experts in the field discuss recent advances that are showing promise in improving patient outcomes in metastatic pancreatic cancer.

Q:

What recent advances are showing promise in improving outcomes for patients with metastatic pancreatic cancer?

Michael Morse, MD, MHS, FACP

Professor of Medicine, Division of Medical Oncology
Professor, Department of Surgery
Duke University Medical Center
Durham, NC

The fact that we now have a US Food and Drug Administration (FDA)–approved second-line therapy, nanoliposomal irinotecan, is very important to the field. It starts you thinking about multiple lines of therapy for patients and what the first-line therapy should be if you’re considering multiple lines of therapy. In addition, there are some fascinating things starting to arise. One that has been around for a little while but seems to be making its rounds to pancreatic cancer with some possible activity is asparaginase encapsulated in erythrocytes. When combined with gemcitabine + nab-paclitaxel, it seems to have some almost surprising survival benefit, so I assume we are going to see more of that come down the line. It has not been super effective in other scenarios, but I think we have to take each tumor on its course. We know that asparagine synthase is up-regulated in some of the microarray studies that have been done, so it may really be relevant in pancreatic cancer. In another area, for the minority of patients that actually have microsatellite instability, there is at least the possibility of treating them with anti-PD-1 therapy. In addition, there is the idea of myeloid-derived suppressor cells (MDSCs) being a component of the immunosuppressive environment and continued studies with CCR2 inhibition along with chemotherapy that seem to be showing some early-phase evidence of activity. Lastly, there is antitumor activity of PEGylated human IL-10 (AM0010) and activity in the second line with a pivotal trial going on right now with that combination with chemotherapy. In summary, I am excited in many ways about the new treatments coming along, and second-line therapy available as well.

“The fact that we now have an FDA-approved second-line therapy, nanoliposomal irinotecan, is very important to the field. It starts you thinking about multiple lines of therapy for patients and what the first-line therapy should be if you’re considering multiple lines of therapy.”

Michael Morse, MD, MHS, FACP

Alok Khorana, MD

Professor of Medicine
Director, Gastrointestinal Malignancies Program
Cleveland Clinic
Cleveland, OH

There has been a lot of nihilism about the treatment of pancreatic cancer, certainly between the mid-1990s and now, with multiple randomized clinical trials failing in the phase III setting. Generally speaking, there is optimism now coming from the high response rates that we are seeing because we now have combination regimens and treatment options along with the approval of a second-line regimen that includes nanoliposomal irinotecan, and we are now thinking about sequencing treatments in patients with metastatic pancreatic cancer. We also have evolving new technology, such as the use of stereotactic body radiation therapy (SBRT) in this setting. So, I think there is certainly more promise shown now than we have seen in decades with the approval of new agents, the ability to sequence because we have choices of regimens, and the advent of combination chemotherapy. There is even a newer sliver of hope with the use of immunotherapy, which only applies to a small section of patients with pancreatic cancer, but the early data look very promising, and pancreatic cancer is also including in the latest FDA approval of immunotherapy for patients with advanced solid tumors that have high microsatellite instability.

“Generally speaking, there is optimism now coming from the high response rates that we are seeing because we now have combination regimens and treatment options along with the approval of a second-line regimen that includes nanoliposomal irinotecan, and we are now thinking about sequencing treatments in patients with metastatic pancreatic cancer.”

Alok Khorana, MD

Thomas A. Abrams, MD

Assistant Professor of Medicine
Harvard Medical School
Senior Physician
Dana-Farber Cancer Institute
Boston, MA

With the kinds of things that we have been looking at in pancreatic cancer, including the role of BRCA mutations, I think we are increasingly recognizing that some percentage—8% to 10%—of patients with pancreatic cancer harbor deleterious BRCA mutations, and based on data in other diseases, PARP inhibitors may play a role either as direct treatment or as maintenance. I think that is a really interesting advance that might be helping patients in the very near future because those drugs are already approved. Although the new molecular approaches are fascinating, it is critical not to underestimate the advances of chemotherapy itself. Chemotherapy is still the cornerstone of treatment for pancreatic cancer and certainly has improved outcomes very significantly for patients.

“Although the new molecular approaches are fascinating, it is critical not to underestimate the advances of chemotherapy itself. Chemotherapy is still the cornerstone of treatment for pancreatic cancer and certainly has improved outcomes very significantly for patients.”

Thomas A. Abrams, MD

References

Aprile G, Negri FV, Giuliani F, et al. Second-line chemotherapy for advanced pancreatic cancer: Which is the best option? Crit Rev Oncol Hematol. 2017;115:1-12.

Gupta R, Amanam I, Chung V. Current and future therapies for advanced pancreatic cancer. J Surg Oncol. 2017;116(1):25-34.

Sohal DPS, Willingham FF, Falconi M, et al. Pancreatic adenocarcinoma: improving prevention and survivorship. Am Soc Clin Oncol Educ Book. 2017;37:301-310.

Wang-Gillam A, Li CP, Bodoky G, Dean A, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016;387(10018):545-557.

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