Efficacy of nanoliposomal irinotecan in metastatic pancreatic ductal adenocarcinoma: A meta-analysis of NAPOLI randomized clinical trials.

Abstract

e16429 Background: Nanoliposomal irinotecan (Nal-IRI) is a DNA topoisomerase I inhibitor that recently showed promising results for the treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC), when used in combination with other chemotherapeutic regimens [5-fluorouracil (FU), leucovorin (LV), or oxaliplatin (OX)]. Our study aims to analyze the efficacy of Nal-IRI for mPDAC treatment in phase III clinical trials. Methods: We collected data through a systemic search of PubMed, EMBASE, and Clinitaltrials.gov, using MeSH terms for mPDAC and Nal-IRI, through December 2024. The initial search yielded 233 articles. After excluding duplicates and irrelevant articles, we included two NAPOLI phase III randomized clinical trials (RCTs) reporting Nal-IRI efficacy in mPDAC. Odds ratio (OR) of overall response rate (ORR) and hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) were computed along with a 95% confidence interval (CI) and p-value for pooled analysis using RevMan v.5.4. Results: NAPOLI-1 evaluated the efficacy of Nal-IRI + FU + LV (n = 117) vs FU + LV (n = 119) in patients with mPDAC with a median follow-up of 13.1 months (mo). NAPOLI-3 evaluated the efficacy of Nal-IRI + FU + LV + OX (n = 383) vs nab-paclitaxel + gemcitabine (n = 387) in patients with mPDAC with a median follow-up of 16.1 mo. Nal-IRI dose was 80 mg/m 2 in NAPOLI-1 and 125 mg/m 2 in NAPOLI-3 clinical trial. A total of 1006 patients were evaluated in NAPOLI-1 and NAPOLI-3 RCTs. We analyzed 500 patients as part of the intervention group (Nal-IRI containing regimen) and 506 patients as part of the control group (FU+LV or nab-paclitaxel + gemcitabine regimen). A pooled analysis revealed significantly improved ORR in Nal-IRI group vs control group with an OR of 1.50 (95% CI: 1.1.4-1.97) (P = 0.004). Overall survival was reported to be 18% higher in the Nal-IRI group vs control group (8.65 vs 6.70 mo) with HR of 0.82 (CI: 0.71-0.94] (P = 0.004). OS rate at 6 mo [OR: 1.52, (95% CI: 0.98-2.35) (P = 0.06)] and OS rate at 12 mo [OR: 1.52 (95% CI: 0.98-2.35) (P = 0.06)] showed a trend towards improvement in Nal-IRI group vs control. Significantly improved results were observed for PFS for Nal-IRI group vs control group (5.25 vs 3.55 mo) with HR of 0.66 (95% CI: 0.57-0.77) (P < 0.05). Nal-IRI-based regimens trended towards increased risk of grade ≥3 adverse events [HR: 1.08 (95% CI: 0.99- 1.17) (P = 0.08)] vs control group, with an increased risk of diarrhea [relative risk (RR): 3.96 (95% CI: 2.55-6.16) (P < 0.00001)], but a statistically non-significant decreased risk of neutropenia [RR: 0.95 (95% CI: 0.73-1.24) (P = 0.70)]. Conclusions: Nal-IRI addition to standard chemotherapeutic regimens (FU+LV, FU+LV+OX) for mPDAC, achieved improved efficacy in terms of ORR, OS, and PFS with a manageable toxicity profile, providing a benchmark for future studies.