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.

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.