Efficacy and tolerability of the combination of nano-liposomal irinotecan and 5-fluorouracil/leucovorin in advanced pancreatic adenocarcinoma: post-approval clinic experience

Nano-liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) is the regimen of choice in the 2 line setting for advanced pancreatic adenocarcinoma (PAC). However, real-world data is limited. Our objectives were to elicit the real-word effectiveness and safety of this combination as an advanced line of therapy in pancreatic cancer patients and analyze the impact of prior lines of therapy on survival outcomes with this regimen. We conducted a retrospective cohort study of 58 patients with locally advanced unresectable or metastatic PAC, who were treated with at least one dose of nal-IRI + 5-FU/LV following cancer progression on prior therapies between August 2015 and December 2018 at the Kansas University Medical Center (KUMC) and University of Alabama at Birmingham (UAB). Median OS was 5.4 (range, 4.2-7) months. Disease control rate (DCR) was highest (84%) for patients given nal-IRI + 5-FU/LV as 2 line agent after progression on a 1 line gemcitabine-based regimen. However, no significant survival difference was observed between those given nal-IRI + 5-FU/LV after 1 line or beyond the 2 line (P=0.17). Among those given nal-IRI + 5-FU/LV as 2 line, use of gemcitabine-inclusive chemotherapy as the 1 line agent did not impact survival (P=0.68). Prior irinotecan exposure and baseline CA 19-9 level did not affect the overall survival (OS) but patients with a higher CA 19-9 level had a significant risk of progression (HR =3.2, P=0.02). Grade 3/4 toxicities were reported in only 19% patients. Our report suggests that nal-IRI + 5-FU/LV offers a modest survival benefit with a tolerable safety profile as an advanced line of treatment in patients with advanced PAC.