patient care perspectives

Selecting Second-Line Treatment Options in Patients With Metastatic Pancreatic Cancer

by Philip A. Philip, MD, PhD, FRCP


Due to improved treatment with newly approved first-line combination treatments in metastatic pancreatic cancer, treatment patterns now demonstrate that approximately half of the patients now go on to receive second-line therapy. Currently, there is no definitive second-line standard of care. The clinical practice guidelines of the American Society of Clinical Oncology (ASCO) recommend that gemcitabine + albumin-bound paclitaxel (nab-paclitaxel) be given as second-line treatment to patients receiving first-line treatment with FOLFIRINOX*. If a patient receives a gemcitabine-based regimen first-line, ASCO recommends the following: liposomal irinotecan in combination with 5-FU and leucovorin (5-FU/LV) (an FDA-approved treatment option), FOLFIRINOX, or if a patient’s comorbidity profile prohibits aggressive regimen, gemcitabine or 5-FU can be considered. A member of our expert panel explains how to best determine second-line therapy in clinical practice.

 *FOLFIRINOX: FOL=leucovorin calcium (folinic acid); F=5-fluorouracil; IRIN=irinotecan hydrochloride; OX=oxaliplatin.

Expert Commentary

Philip A. Philip, MD, PhD, FRCP

Professor of Oncology and Internal Medicine
Vice President for Medical Affairs
Barbara Ann Karmanos Cancer Institute
Wayne State University School of Medicine
Detroit, MI

Certainly, we are now seeing more patients receiving second-line treatment. As for the numbers, if you are working in an academic institution, you are seeing more second-line treatment, and in my opinion, probably more than 50%. Whereas in the community setting, I think that number is a bit lower because of the type of patients and use of a different treatment approach. Second-line treatment options depend on what patients received in the front line, and that is how we make the decision for the second line. We also take into account performance status, and we look at some residual side effects that may affect the choice of treatment. If someone received chemotherapy up front and then had significant neurotoxicity, we possibly have to be careful in using a drug that causes neurotoxicity. Obviously, here we have only 2 drugs we are dealing with: liposomal irinotecan or nab-paclitaxel, which can cause neuropathy.

 In second-line patients who receive gemcitabine + nab-paclitaxel as front-line therapy, second-line therapy will be based on treatment tolerability and specific patient characteristics, with liposomal irinotecan combined with 5-FU/leucovorin or FOLFIRINOX both being good clinical options for second-line therapy. In patients who receive FOLFIRINOX as front-line, they would receive gemcitabine + nab-paclitaxel as second-line, with liposomal irinotecan + 5-FU/leucovorin as a third-line option, if they do not have any significant neuropathy and are well enough to receive the combination treatment.


Abrams TA, Meyer G, Meyerhardt JA, Wolpin BM, Schrag D, Fuchs CS. Patterns of chemotherapy use in a U.S.-based cohort of patients with metastatic pancreatic cancer. Oncologist. May 5, 2017. doi: 10.1634/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, Goto A, Endo I, Ichikawa Y. 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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