Eileen M. O'Reilly, 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?

An important development in the field has been the identification of a new reference regimen in a second-line setting. This is the first time we’ve seen a phase III trial being positive in this setting in pancreas cancer, so that represents an important milestone. It’s also a reference for drug development and for comparison in terms of what the benchmarks are for your new therapy as you’re developing it in a second-line disease setting. The regimen comprised of liposomal irinotecan, 5-FU, and leucovorin is given on an outpatient basis over a couple of hours in the clinic and then via an infusion at home, cycled every two weeks.

Toxicities are, as you might expect from the components, primarily fatigue, diarrhea, neutropenia, risk of infection, and gastrointestinal toxicities in terms of nausea and vomiting. Because this drug is an irinotecan derivative, there can be cholinergic-related side effects. So, sometimes as we administer it or shortly after, people will get cramping and salivation and benefit thereafter from pre-medicating with atropine, and that essentially mitigates that early salivation, diarrhea, discomfort that patients feel.

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.