Glassman DC, et al. ASCO GI 2018:471

A retrospective study of nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer


The phase III NAPOLI-1 trial demonstrated the efficacy of nanoliposomal irinotecan in combination with 5-fluorouracil and leucovorin (nal-IRI plus 5-FU/LV) in patients with advanced pancreatic adenocarcinoma (PDAC) following progression on gemcitabine-based therapy.1 However, safety and efficacy data following the U.S. Food and Drug Administration approval of nal-IRI plus 5-FU/LV are limited. At ASCO GI 2018, the safety, tolerability, and efficacy of nal-IRI plus 5-FU/LV was retrospectively assessed in patients with advanced PDAC at Memorial Sloan Kettering Cancer Center (MSKCC).2

Study design

  • A retrospective chart review was performed for all patients at MSKCC with advanced PDAC treated with nal-IRI plus 5-FU/LV between October 2015 and June 2017.
  • A total of 56 patients identified through electronic medical records were included in the study.
  • Safety was evaluated through collection of all treatment-related adverse events (AEs) and serious adverse events (SAEs) that occurred during nal-IRI plus 5-FU/LV treatment.
  • All AEs were graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
  • Response to nal-IRI plus 5-FU/LV per Response Evaluation Criteria in Solid Tumors version 1.1 was assessed by computed tomography (CT) every 8–12 weeks.
  • Patients without progression or death were censored at the last follow-up date as of November 2, 2017.

Key findings

Baseline characteristics

  • The median age of patients was 68 years (range: 42–88).
  • The majority of patients had stage IV disease (96%) and an Eastern Cooperative Oncology Group performance status score of 1 (73%).
  • Half of patients had their primary tumour located in the head of the pancreas (28 patients).
  • The most frequently observed metastatic sites were in the liver (73%), distant lymph nodes (32%), peritoneum (29%), and lung (27%).
  • Sixteen patients (29%) had three or more metastatic sites and 11 patients (20%) had three or more prior lines of advanced disease therapy.

Safety and tolerability

  • The most frequently reported AEs in this retrospective study were anemia (89%), fatigue (80%), and diarrhea (63%).
  • Frequencies of AEs were comparable between advanced PDAC patients treated with nal-IRI plus 5-FU/LV at MSKCC and those treated in the NAPOLI-1 trial, with the exception of fatigue and anemia which occurred more frequently in the patients treated at MSKCC (80% vs. 40% and 89% vs. 38%, respectively). (Table 1)
  • The starting dose of nal-IRI was ≤50 mg/m2 in 23 patients (41%), 55 mg/m2 in nine patients (16%), 60 mg/m2 in seven patients (13%), and 70 mg/m2 in 17 patients (30%).
  • For 38 patients, reductions of nal-IRI dose were not required.
    • One dose reduction occurred in 15 patients and three patients required two dose reductions of nal-IRI.
    • The most common reasons for dose reduction were fatigue (8 patients) and diarrhea (8 patients).

Table 1. Adverse events


  • Response rates were as follows:
    • Partial response, 5%;
    • Stable disease, 41%; and
    • Progressive disease, 41%.
  • Seven patients (13%) were not evaluable for response.
  • Of the 44 patients evaluable for carbohydrate antigen 19-9 response (CA19-9, maximal response/baseline), 19 patients (34%) experienced an increase in CA19-9 levels, 15 patients (27%) experienced a CA19-9 reduction between 0% and 50%, and 10 patients experienced a >50% CA19-9 reduction.
  • The median progression-free survival (PFS) was 2.9 months and the median overall survival (OS) was 5.3 months.
  • PFS and OS of patients treated with nal-IRI plus 5-FU/LV, stratified by line of therapy are presented in Figure 1.
  • PFS and OS of patients treated with nal-IRI plus 5-FU/LV, stratified by prior irinotecan treatment are presented in Figure 2.

Figure 1. PFS and OS stratified by line of therapy

Figure 2. PFS and OS stratified by prior irinotecan treatment

Key conclusions

  • Data from patients with advanced PDAC treated with nal-IRI plus 5-FU/LV at MSKCC reinforce the results of the NAPOLI-1 trial and support the safety and efficacy of this treatment.
  • Patients without disease progression on prior irinotecan therapy had significantly better survival outcomes than patients with progression, when treated with nal-IRI plus 5-FU/LV.
  • Studies to identify predictive markers of treatment response are ongoing.
  • The findings of the study underscore the benefit of nal-IRI plus 5-FU/LV following nanoparticle albumin-bound paclitaxel with gemcitabine for patients with advanced PDAC.

References: 1. Wang-Gillam A, Li C-P, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet 2016:387(10018):545–57. 2. Glassman DC, Palmaira RL, Covington CM, et al. Nanoliposomal irinotecan with flurouracil for the treatment of advanced pancreatic cancer.  J Clin Oncol (ASCO GI Annual Meeting) 2018;36(Suppl): abstr 471.