Impact of prior conventional irinotecan use on nanoliposomal irinotecan efficacy in advanced pancreatic cancer: a meta-analysis.

BACKGROUND

Nanoliposomal irinotecan (nal-IRI) has become an established therapy for advanced pancreatic ductal adenocarcinoma (PDAC), both in the post-gemcitabine setting and, more recently, in the first-line NALIRIFOX regimen. Concerns remain regarding cross-resistance in patients previously exposed to conventional irinotecan. We performed a systematic review and meta-analysis to evaluate the impact of prior irinotecan exposure on outcomes with nal-IRI.

MATERIALS AND

METHODS

We conducted a systematic literature search of PubMed, Embase, and the Cochrane Library through July 2025 following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Eligible studies included patients with advanced PDAC treated with nal-IRI-containing regimens and reported outcomes stratified by prior irinotecan exposure. Data extraction and risk of bias assessments were performed independently by two reviewers. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled using random-effects models. Sensitivity and publication bias analyses were conducted.

RESULTS

Thirteen retrospective studies comprising 2271 patients were included. One-third (33.1%) had received conventional irinotecan before nal-IRI. Prior irinotecan exposure was associated with inferior outcomes: pooled unadjusted and adjusted HRs for OS were 1.48 [95% confidence interval (CI) 1.24-1.76, P = 0.001] and 1.42 (95% CI 1.03-1.96, P = 0.030), respectively. For PFS, pooled unadjusted and adjusted HRs were 1.45 (95% CI 1.28-1.64, P < 0.001) and 1.72 (95% CI 1.16-2.54, P = 0.007), respectively. Patient-level subgroup analyses indicated that patients discontinuing prior irinotecan due to progression had significantly worse OS compared with those discontinuing for other reasons (HR 1.97, 95% CI 1.10-3.52). Most studies were high quality, and sensitivity analyses confirmed the robustness of the findings.

CONCLUSION

Prior exposure to conventional irinotecan, particularly discontinuation for progression, reduced clinical benefit from subsequent nal-IRI therapy in advanced PDAC in observational cohorts. These findings support caution when considering nal-IRI soon after irinotecan progression and highlight the need for prospective sequencing studies.