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

Abstract

The majority of pancreatic cancers are diagnosed at an advanced stage, when surgical options are limited and treatment relies on systemic chemotherapy. In the NAPOLI-1 trial, liposomal irinotecan in combination with fluorouracil (nal-iri/5FU) was shown to improve overall survival when compared to fluorouracil alone for metastatic pancreatic cancer. Other retrospective studies have shown the combination of fluorouracil and conventional irinotecan (FOLFIRI) to be a viable option, though no randomized trials have compared nal-iri/5FU to FOLFIRI. The purpose of this single-center, retrospective, cohort study was to determine if nal-iri/5FU and FOLFIRI are similarly effective for the treatment of advanced pancreatic cancer. Due to the potential for treatment bias, inverse probability of treatment weighting was utilized to correct for baseline differences between the groups. The primary outcome of progression-free survival was similar at 4.1 months for nal-iri/5FU and 3.1 months for FOLFIRI. Overall survival and adverse effect frequency were also similar. Pegfilgrastim was used in 16% and 15% of patients, respectively, and nal-iri/5FU patients required significantly less atropine during treatment (36 vs. 70%). A cost analysis was conducted and concluded that the treatment with nal-iri/5FU was nearly 30 times more expensive than FOLFIRI treatment. Together, these data suggest a potential role for FOLFIRI for the treatment of advanced pancreatic cancer in the absence of clear benefits in effectiveness, toxicity, or cost for nal-iri/5FU.

Liposomal Irinotecan: A Review in Metastatic Pancreatic Adenocarcinoma

“…Prior to the approval of nal-IRI + 5-FU/LV, the most commonly employed regimens for the treatment of gemcitabine-pretreated PDAC were 5-FU/LV in combination with either conventional irinotecan (FOLFIRI) or oxaliplatin-based treatment (FOLFOX; OFF), albeit these regimens were supported by no (FOLFIRI) or conflicting (FOLFOX; OFF) data from randomized phase III trials [ 25 ]. Retrospective, single-centre observational studies suggest survival outcomes with nal-IRI + 5-FU/LV are at least comparable to those with FOLFIRI [ 51 ] or FOLFOX [ 24 ], and prospective, randomized, multicentre comparisons of these regimens would be of interest.…”

Comparing real-world evidence among patients with metastatic pancreatic ductal adenocarcinoma treated with liposomal irinotecan

“…The search strategy yielded 81 studies, 75 of which were excluded according to the criteria presented in Figure 1 . The remaining six publications – Glassman et al ., 10 Barzi et al ., 11 Ahn et al ., 12 Tossey et al ., 13 Kieler et al ., 14 and Yoo et al . 15 – were included in this analysis.…”

“… a Tossey et al . 13 report nausea and vomiting as one AE. AE, adverse event; NR, not reported; RWE, real-world evidence …”

“…Tossey et al was a single-center, retrospective, cohort study that analyzed RWE available for patients with mPDAC aged 18–89 years and treated with liposomal irinotecan + 5-FU/LV therapy at The Ohio State University Comprehensive Cancer Center, James Cancer Hospital, and Solove Research Institute from October 2015 to August 2018. 13 PFS, defined as the time from the first dose of chemotherapy to disease progression or death, was the primary outcome of the study. Secondary outcomes were TTF, OS, frequency of dose reductions or treatment delays, and frequency of AEs.…”

“…Eligibility criteria included previous gem-based therapy, either as the first-line treatment of unresectable or metastatic disease, or as either neoadjuvant or adjuvant treatment if within the preceding 6 months. 13 …”