George P. Kim, MD: The Significance of Second-Line Therapy in Pancreatic Cancer

What is the significance of having a second-line therapy for pancreatic cancer, and what type of efficacy can be expected with the nanoliposomal irinotecan regimen in this setting? What are your experiences with toxicities with this agent?

The significance of having a second-line treatment in metastatic pancreatic cancer, for old guys like me, is that in the old days, we just had gemcitabine. We didn’t have options and active treatments like we do now. And remember, these are metastatic pancreatic cancer patients. These are the most courageous people you’re going to meet, and now we have treatments available to them. The importance of Onivyde/nal-IRI in this setting is that we have a therapy should they have progression or the treatment doesn’t continue to work in the frontline, that being a gemcitabine-based treatment, typically gemcitabine/nab-paclitaxel. It’s of historic importance that we have another treatment.

Now, this drug is very novel in that it is 80,000 irinotecan molecules in a liposome. It’s a nanoparticle. Its circulation throughout the body is prolonged up to two to four-fold, not only of the irinotecan but also of the active moiety, active metabolite, SN-38. It’s very important that the drug and the active metabolite circulate throughout the body for a longer period of time. Ninety-five percent of the drug stays in the liposome.

This is a very important regimen that we have available to us. The good news is the toxicities are very similar to the irinotecan experience that we’ve previously had in colorectal cancer, meaning the major side effects are diarrhea, which any GI oncologist, even myself, can manage. You need to give atropine, you need to give your Imodiums and your Lomotils, but you really know how to manage this already. Then the other toxicity is neutropenia.

Metastatic Pancreatic Cancer: Case 1

Larry D, a 62-year-old, presented to his primary care physician with persistent pain in his epigastric region, which persists throughout the night. Within the past 2 years, he has developed diabetes and experienced considerable weight loss with signs of depression.

• During his visit, jaundice was observed along with periumbilical subcutaneous metastases.
• Testing revealed an elevated CA19-9 level (2293 U/ml).
• CT scan showed a large mass on the head of the pancreas, and a subsequent biopsy showed the mass to be adenocarcinoma. Liver and local lymph note metastases were identified.

Larry went on to receive the combination of nab-paclitaxel and gemcitabine as frontline therapy for 5 months:

• Upon progression, Larry was switched to the combination of liposomal irinotecan, fluorouracil, and folinic acid. Treatment failure occurred after 2.5 months.
• Larry received FOLFOX as a third-line treatment.