Sequencing Strategies: Metastatic Pancreatic Adenocarcinoma - Episode 3

Sequencing Strategies in Pancreatic Cancer


Fadi Braiteh, MD: Despite a very grim prognosis in stage 4 pancreatic cancer, it’s exciting that we’re bringing 2 new modalities onboard in the frontline setting that are standard of care. We even have a second-line, post-gemcitabine standard-of-care treatment option—nanoliposomal irinotecan. It’s FDA approved for post-gemcitabine advanced pancreatic cancer, metastatic or not, in combination with fluorouracil (5-FU) and leucovorin. This is the only FDA-approved drug in that setting. It’s category 1 in the National Comprehensive Cancer Network guidelines. It’s a great opportunity. We have really moved forward from 5 years ago when thinking about advanced pancreatic cancers. When it came to systemic therapy, we had 1 shot at this disease. Now there is first-line therapy, second-line therapy, and we have many clinical trials that are even looking beyond the second-line setting. We’re moving a bit to where pancreatic cancer may join the club with colorectal cancer, lung cancer, and, maybe, breast cancer. We’re not quite there in efficacy, but we’re moving the needle, as well.

This is crucial, and it’s important to discuss these options with patients. There are data showing the percentage of patients who needed to be on second-line therapy in pancreatic cancer about 10 years ago. That number doubled in recent years. In part, it’s because of the advance of supportive care. I give credit for this to, maybe, earlier diagnoses and aggressive management with the newer drugs and regimens that are onboard. It is crucial to really think about it like a chess game. Don’t just think about the immediate move or immediate line of therapy, but what will be, subsequently. Having the option of using the NAPOLI regimen, the nanoliposomal irinotecan post-gemcitabine, personally swayed me more to use the gemcitabine-based regimen in the frontline setting.

John L. Marshall, MD: We never, ever thought that we’d be thinking about second-line pancreas cancer. Now, frankly, we’re thinking about third-line pancreas cancer in some patients. It’s interesting—different places have different feelings about this. In some more rural, maybe less well educated populations, people show up being pretty sick to start with. They often don’t make it into the second- or third-line setting. Now the majority of patients are of a good-enough performance status. The diagnosis has been made early enough. We can think about lines of therapy just like we did with colorectal cancer, where we said it mattered to get all of the medicines. We don’t have a biomarker to tell you which one to take and which one to not take. I want to try them all.

So, now I’m thinking about sequential therapy. You really have 2 strategies that you can go with. You can go with a 5-FU—based regimen. That would typically be FOLFIRINOX, first-line, or gemcitabine-based therapy, first-line. But, either way, you can then go to subsequent lines of therapy. Newer approvals with 5-FU–based therapy in second-line and beyond have really shifted my way of thinking—to initiate with gemcitabine-based therapy first, and then use 5-FU–based therapy second. In different patients, we make different decisions. But, in general, and when thinking about sequential therapy, I want to give gemcitabine-based therapy and 5-FU–based therapy, usually in that order.

Transcript Edited for Clarity