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
- 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.
- 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).
- 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.
- 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.