Clinical outcomes of liposomal irinotecan in patients with advanced pancreatic cancer previously treated with conventional irinotecan: A meta-analysis of real-world evidence

Background: Pivotal clinical trials supported survival benefits of liposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin in patients with pancreatic ductal adenocarcinoma (PDAC) who previously received gemcitabine-based therapy. There are concerns about the benefits of nal-IRI in patients who received FOLFIRINOX (combined fluorouracil, leucovorin, IRI, and oxaliplatin) because of potential cross-resistance to IRI. The objective of this meta-analysis was to characterize the impact of the previous receipt of IRI on the outcomes of nal-IRI regimens in patients with advanced PDAC. Methods: Real-world studies evaluating the outcomes of nal-IRI in patients who had prior IRI exposure published up to April 2023 were searched using electronic databases. The meta-analysis was conducted using a random effects model to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Eight studies (n = 1368 patients) were included. The pooled median progression-free survival (PFS) was 2.02 months (95% CI, 1.43–2.57 months), and the median overall survival (OS) was 4.26 months (95% CI, 3.03–5.39 months). Patients with prior IRI exposure had PFS (HR, 1.17; 95% CI, 0.94–1.47; p =.17) and OS (HR, 1.16; 95% CI, 0.95–1.42; p =.16) comparable to patients without prior IRI exposure. Likewise, patients who had progressive disease on conventional IRI had PFS (HR, 1.50; 95% CI, 0.73–3.08; p =.24) and OS (HR, 1.70; 95% CI, 0.68–4.27; p =.26) with nal-IRI comparable to patients who had no progressive disease. Conclusions: Prior IRI exposure does not affect the survival outcomes of nal-IRI regimens in patients who have advanced PDAC. The selection of later lines of chemotherapy regimens should be based on the differential safety profile, patient status, the cost of treatment, and health-related quality of life.