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

Abstract

Background: Nano-liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) is the regimen of choice in the 2 nd line setting for advanced pancreatic adenocarcinoma (PAC). However, realworld 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. Methods: 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).Results: 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 nd line agent after progression on a 1 st line gemcitabine-based regimen. However, no significant survival difference was observed between those given nal-IRI + 5-FU/LV after 1 st line or beyond the 2 nd line (P=0.17). Among those given nal-IRI + 5-FU/LV as 2 nd line, use of gemcitabineinclusive chemotherapy as the 1 st 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.Conclusions: 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.

Effect of previous conventional irinotecan treatment in patients with pancreatic cancer being treated with liposomal irinotecan plus 5‐fluorouracil and leucovorin

“…The NAPOLI-1 study and real-world analyses had confirmed that nal-IRI+5-Fu/LV is an effective chemotherapeutic regimen in patients with mPDAC after gemcitabine-based treatment. 7,[9][10][11][12][13][14][15][16][17] As gemcitabine-based and FOLFIRINOX regimens are both established first-line treatments for mPDAC, nal-IRI+5-FU/LV is often utilized as the second-line or third-line treatment for metastatic pancreatic cancer depending on the previously prescribed chemotherapeutic agents. As a result, patients who received nal-IRI+5-FU/LV in a later treatment line inevitably have poor survival outcomes as opposed to those receiving the same treatment in an earlier treatment line.…”

“…Recent real-world studies have reported a poor survival outcome of nal-IRI+5-FU/LV therapy in mPDAC patients previously treated with conventional irinotecan therapy. [10][11][12] Limited by the small number of patients, all of these studies used univariate analysis to evaluate the effect of conventional irinotecan treatment on nal-IRI+5-FU/LV therapy. [10][11][12] As a result, these results have been criticized for the heterogeneity of patient F I G U R E 3 Overall survival (A) and time-to-treatment failure (B) according to previous conventional irinotecan treatment or non-treatment after propensity score matching.…”

“…9 Consistent with the results of NAPOLI-1, recent real-world studies reported that OS is generally poor in mPDAC patients previously treated with conventional irinotecan compared with those not previously exposed to conventional irinotecan. [10][11][12] Because the irinotecan treatment in mPDAC patients receiving nal-IRI+5-FU/LV by analyzing a population-based dataset.…”

Liposomal irinotecan pre-emptive dose reduction in patients with pancreatic ductal adenocarcinoma: 667 patients’ experience within a population-based study

“…15 Several real-world studies have reported similar results, demonstrating that previous irinotecan treatment was a poor prognostic variable for patients receiving nal-IRI treatment. [17][18][19][20] The same concept applies to patients with previous exposure to 5-FU, which might also compromise the efficacy of nal-IRI + 5-FU/LV treatment.…”

“…15 Several studies have reported real-world data on the clinical efficacy and toxicity of nal-IRI + 5-FU/LV in comparable settings. 16–23 These published studies have reported the common practice of pre-emptive nal-IRI dose reduction to achieve better tolerability and safety profiles without compromising treatment efficacy. 20,21 However, these studies were limited by a single institute experience and small numbers of patients.…”