Post-gemcitabine therapy for patients with advanced pancreatic cancer – A comparative review of randomized trials evaluating oxaliplatin- and/or irinotecan-containing regimens

• Post-gemcitabine advanced pancreatic cancer patients have limited treatment options.
• Head-to-head comparisons of common oxaliplatin-based regimens are not available.
• Randomized oxaliplatin- and irinotecan-based chemotherapy trials were reviewed.
• Differences noted in study design, patient/treatment characteristics, and outcomes.
• Evaluated studies were dissimilar, precluding an indirect treatment comparison.

A systematic review and critical evaluation of randomized trial evidence for oxaliplatin- or irinotecan-containing regimens in patients with advanced pancreatic cancer previously treated with gemcitabine has not yet been published. We conducted a comparative systematic review of randomized trials evaluating oxaliplatin- or irinotecan-based therapies in patients with advanced pancreatic cancer previously treated with gemcitabine to assess trial similarity and the feasibility of performing an indirect treatment comparison (ITC). Studies were identified through PubMed and key oncology conference abstracts. The following trials met our criteria: NAPOLI-1 (nanoliposomal irinotecan [nal-IRI] or nal-IRI + 5-fluorouracil [5-FU]/leucovorin [LV] vs 5-FU/LV), CONKO-003 (oxaliplatin + 5-FU/LV [OFF] vs 5-FU/LV), PANCREOX (oxaliplatin + 5-FU/LV [mFOLFOX6] vs 5-FU/LV), and Yoo et al. (2009) (irinotecan + 5-FU/LV [mFOLFIRI3] vs mFOLFOX). Fundamental differences were identified in study design (i.e., number of study sites, number of countries), patient (i.e., locally advanced vs metastatic disease, stratification variables, prior and subsequent treatments) and treatment (i.e., regimens, dose intensity) characteristics, and primary and secondary outcomes (i.e., primary vs secondary outcomes, overall survival [OS], progression-free survival [PFS]) among the 4 included trials. Our comparative review demonstrated significant dissimilarity across trials, which precluded conducting an ITC. In the absence of head-to-head nal-IRI- and/or oxaliplatin-based therapy trials, clinicians are advised to interpret these studies separately within the context of their individual patient population.