1680P - Meta-analysis of real-world survival outcomes of liposomal irinotecan in advanced pancreatic cancer patients with prior irinotecan exposure

Background

Liposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/leucovorin (LV) demonstrated survival benefits in advanced pancreatic cancer (APC) patients (pts) who progressed on gemcitabine-based therapy. The NAPOLI-1 demonstrated greater survival benefits from nal-IRI+5-FU/LV in IRI-naïve pts. Nal-IRI may be less effective in pts with prior irinotecan (IRI) exposure due to a potential cross-resistance to SN-38. This raised concerns about the relevance of nal-IRI + 5-FU/LV in clinical practice, as FOLFIRINOX is the recommended first-line regimen for APC pts with good performance status. Therefore, we evaluated the real-world survival outcomes of nal-IRI in patients with prior IRI exposure.

Methods

Real-world studies evaluating the outcomes of nal-IRI in pts with prior IRI exposure published up to April 2023 were searched using electronic databases including PubMed, Scopus, Cochrane CENTRAL, Web of Science, EBSCOhost. The meta-analysis was conducted using the R package v4.3.0 and RevMan v5.4.1. Random effects model was used to estimate the pooled hazard ratio (HR) and the 95% confidence interval (CI). I² statistics was obtained to evaluate the heterogeneity of the studies.

Results

Out of the total 470 pts from seven studies that are included in the meta-analysis, most pts with prior IRI exposure received nal-IRI at the third or later lines. The pooled median progression-free survival (PFS) and overall survival (OS) were 1.9 (95% CI: 1.4-2.4) and 4.1 months (95% CI 3.4-4.7), respectively. The pts with prior IRI exposure had comparable PFS (pooled HR 1.20, 95% CI 0.67-2.14, p= 0.53, I²= 0%) and OS (HR 1.13, 95% CI 0.69-1.84, p= 0.63, I²= 0%) to pts without prior IRI exposure. Pts who discontinued prior IRI due to progressive disease had comparable PFS (HR 1.60, 95% CI 0.34, 7.58, p=0.55, I²= 0%) and OS (HR 2.09, 95% CI 0.29, 14.87, p=0.46, I²= 0%) to pts with no progressive disease. Nal-IRI had a manageable safety profile across the included studies.

Conclusions

Prior IRI exposure had no impact on the survival outcomes of nal-IRI-containing regimen in APC pts. Thus, it is feasible to introduce nal-IRI in later lines of treatment in patients with prior IRI exposure. Further prospective studies are warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.