expert roundtables

Course of Treatment in Metastatic Pancreatic Cancer

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

Overview

Newer options exist for the treatment of metastatic pancreatic cancer, and not all of the agents can be used at the same time. Multiple factors are considered when choosing a first-line treatment. Experts note that treatment guidelines are sufficiently adaptable such that patients can essentially begin on any regimen that is appropriate based on performance status and other considerations, and that the full treatment plan flows from the choice of first-line therapy.

Q:

With the newly approved drug therapies for metastatic pancreatic cancer, how do you approach decisions about first-, second-, and third-line therapy?

Alok Khorana, MD

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

The treatment of pancreatic cancer is undergoing a little bit of an evolution. This is partly due to the fact that there are now more drugs approved by the US Food and Drug Administration (FDA) for treating advanced pancreatic cancer than ever before. This is partly driven by the fact that not all of these drugs can be used at the same time. Because there are now new treatments, we have choices in sequencing which drug to use in the first-line, second-line, and third-line treatment. Individual choices can be made, largely based on performance status, comorbidities, goals of care, and willingness to tolerate the toxicity from certain combination regimens. It is good to have choices, but it has also made it harder to definitively say that there is a clear way to sequence treatments in metastatic pancreatic cancer.

Generally speaking, the guidelines of clinical practice are following a similar pathway. For first-line treatment, if you have great performance status and fewer comorbidities, the goals of care are to be aggressive and reduce your pancreatic cancer burden, and FOLFIRINOX is a great way to start. If you’re concerned about toxicity but still want a combination therapy, then gemcitabine + nab-paclitaxel is a great way to start. If the physician or the patient has concerns about quality-of-life, toxicity, comorbidities, or performance status, the single agent gemcitabine is another first-line option. So, you really have 3 first-line options, and you can vary them depending on patient wishes and any concerns about the patient’s ability to tolerate treatment. Generally speaking, for a large majority of patients I think the gemcitabine + nab-paclitaxel combination is the preferred way to start. For second-line therapies, you sequence depending on what was used in the first-line regimen. For example, if you used gemcitabine + nab-paclitaxel, as a majority of patients receive, then going to an irinotecan-based formulation next certainly makes sense. The nanoliposomal irinotecan that was recently FDA approved in combination with 5-fluorouracil (5-FU) and leucovorin is a great choice for second-line therapy. For third-line therapy, clinical guidelines recommend clinical trial participation. Participation in a clinical trial is recommended for first and second-line therapy as well, but when you get to third-line therapy and you’ve exhausted the standards or care, that is an even better time to consider participating in clinical trials.

“Individual choices can be made, largely based on performance status, comorbidities, goals of care, and willingness to tolerate the toxicity from certain combination regimens.”

Alok Khorana, MD

Michael Morse, MD, MHS, FACP

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

In choosing treatment sequencing, you have your option of gemcitabine based, mainly gemcitabine + nab-paclitaxel, or fluoropyrimidine based, mainly FOLFIRINOX, as the front-line treatment option. If you used a gemcitabine-based regimen in the first line, you are going to use fluoropyrimidine based and nanoliposomal irinotecan as second line, and that is certainly appropriate as it is the only FDA-approved regimen in the second line. As for third-line therapy, there is not a study that I am aware of that has addressed the benefit of therapy in third line. In the past, we never had patients go to third-line therapy, but we are starting to see that now. If I think from the beginning that a patient might actually be able to get 3 lines of treatment, typically I have given gemcitabine-based therapy as first line, usually gemcitabine + nab-paclitaxel; 5-FU with nanoliposomal irinotecan as second line; and oxaliplatin-based regimen as third line. But it’s still a minority of patients who actually get to third-line therapy.

“If I think from the beginning that a patient might actually be able to get 3 lines of treatment, typically I have given gemcitabine-based therapy as first line, usually gemcitabine + nab-paclitaxel; 5-FU with nanoliposomal irinotecan as second line; and oxaliplatin-based regimen as third line. But it’s still a minority of patients who actually get to third-line therapy.”

Thomas A. Abrams, MD

References

Abrams TA, Meyer G, Meyerhardt JA, et al. Patterns of chemotherapy use in a U.S.-based cohort of patients with metastatic pancreatic cancer. Oncologist. 2017 May 5. pii: theoncologist.2016-0447. [Epub ahead of print].

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.

Kobayashi N, Shimamura T, Tokuhisa M, et al. Effect of FOLFIRINOX as second-line chemotherapy for metastatic pancreatic cancer after gemcitabine-based chemotherapy failure. Medicine (Baltimore). 2017;96(19):e6769.

Lamb YN, Scott LJ. Liposomal irinotecan: a review in metastatic pancreatic adenocarcinoma. Drugs. 2017;77(7):785-792.

Sohal DP, Mangu PB, Khorana AA, et al. Metastatic pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016;34(23):2784-2796.

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