Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience

Abstract

BackgroundEffective treatment options for advanced pancreatic cancer are finite. NAPOLI-1, a phase III randomized trial, demonstrated the efficacy of nanoliposomal irinotecan with fluorouracil/leucovorin (nal-IRI + 5-FU/LV) for the treatment of advanced pancreatic cancer following progression on gemcitabine-based chemotherapy. There are limited additional data on the safety and efficacy of nal-IRI + 5-FU/LV following FDA approval in October 2015. We examined the post-approval safety and effectiveness of nal-IRI + 5-FU/LV in advanced pancreatic cancer patients receiving treatment at Memorial Sloan Kettering Cancer Center.MethodsA retrospective chart review was conducted of all patients beginning treatment with nal-IRI + 5-FU/LV from October 2015 through June 2017. Using the electronic medical record and institutional database, information was extracted pertaining to demographics, performance status (ECOG), prior therapies, dose, duration of treatment, adverse events, progression free survival (PFS), overall survival (OS) and treatment response.ResultsFifty six patients were identified. Median progression free survival (PFS) was 2.9 months and median overall survival (OS) was 5.3 months. Patients with prior disease progression on irinotecan experienced PFS and OS of 2.2 and 3.9 mo, respectively. Patients without prior irinotecan exposure experienced significantly longer PFS (4.8 mo, p = 0.02) and OS (7.7 mo, p = 0.002), as did patients who received prior irinotecan without disease progression (PFS, 5.7 mo, p = 0.04; OS, 9.0 mo, p = .04). Progression on prior irinotecan was associated with greater lines of prior advanced disease chemotherapy (2 vs 1). Dose reductions (DR) were most frequently due to fatigue (42%) and diarrhea (37%), but were not associated with worse outcomes. In fact, patients with ≥1 DR experienced longer PFS (5.4 v 2.6 mo, p = 0.035). Sequential therapy with nab-paclitaxel + gemcitabine (nab-P + Gem) followed by nal-IRI + 5-FU/LV (n = 25) resulted in OS of 23.0 mo. Mutations in TP53 were associated with shorter PFS.ConclusionsThese data support the safety and efficacy of nal-IRI + 5-FU/LV, reinforcing results of NAPOLI-1. Patients without disease progression on prior irinotecan fared significantly better than patients with progression, when treated with nal-IRI + 5-FU/LV. Sequential therapy with nab-P + Gem followed by nal-IRI + 5-FU/LV demonstrates encouraging median OS. These findings provide guidance for patients most likely to benefit from nal-IRI + 5-FU/LV.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4605-1) contains supplementary material, which is available to authorized users.

Clinical Outcomes of Second-Line Chemotherapy after Progression on Nab-Paclitaxel Plus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma

“…While combining fluoropyrimidine with conventional irinotecan did not show a clear clinical benefit, nal-IRI plus 5-FU/LV significantly improved survival compared with 5-FU/LV, and this regimen received regulatory approval. Recent real-world data showed consistent clinical outcomes with nal-IRI plus 5-FU/ LV in patients with mPDAC who had previously received gemcitabine-based chemotherapy [18,19]. Because of the heterogeneity of 1L chemotherapy prior to the administration of nal-IRI plus 5-FU/LV and different treatment lines (from 1st-to 5th-line) when it was used in those studies, however, it is difficult to estimate the efficacy of 2L nal-IRI plus 5-FU/ LV after 1L nab-P+GEM.…”

Comparison of conventional versus liposomal irinotecan in combination with fluorouracil for advanced pancreatic cancer: a single-institution experience

“…The pre-emptive dose reductions seen in this study represent real-world oncology practices, and compared to prior data this does not seem to have produced significantly poorer outcomes than those seen in clinical trials. Specifically, Glassman and colleagues noted a median starting dose of 55 mg/m 2 for nal-iri in their real-world data study, which was not associated with significantly inferior outcomes [19]. Other studies have shown a similar maintenance of effectiveness for different regimens used in advanced pancreatic cancer despite reductions in dose intensity.…”

“…The phase 3 NAPOLI-1 trial showed PFS for patients treated with nal-iri/5FU to be 3.1 months and OS 6.2 months [18]. More recently, a retrospective real-world experience was published by Glassman and colleagues that reported PFS of 2.9 months [19]. FOLFIRI lacks phase 3 data in this setting, though retrospective and prospective studies can provide estimates of survival outcomes.…”

Impact of New Chemotherapy Regimens on the Treatment Landscape and Survival of Locally Advanced and Metastatic Pancreatic Cancer Patients

“…Supporting these and our findings, also a study by Glassman and colleagues reported promising survival rates for the sequence Gem/NabP followed by FP/Nal-IRI (mOS 23.0 months). They did not find a significant difference to the sequence FOLFIRINOX followed by Gem/NabP and FP/Nal-IRI (mOS 25.5 months) [29]. Furthermore, in the previously mentioned study by Kordes et al patients who received FOLFIRINOX had a shorter median OS (9.9 months, 95% CI; 8.1-11.7) than previously reported [21].…”