Background: Gemcitabine-based and FOLFIRINOX (Oxaliplatin, irinotecan [IRI], 5-fluorouracil [5-FU], and leucovorin [LV]) regimens are common front-line therapies for patients with advanced pancreatic cancer (APC). Later-line options for these patients remain limited. Liposomal irinotecan (nal-IRI) plus 5-FU-LV has demonstrated a survival benefit in APC patients previously treated with gemcitabine-based treatment. However, the efficacy of nal-IRI plus 5-FU-LV in patients previously treated with conventional IRI containing regimens is controversial. Methods: A retrospective chart review was conducted on consecutive APC patients treated at our institution between November 2016 to January 2023 who completed at least one cycle of nal-IRI plus 5-FU-LV and were previously treated with conventional IRI. Data regarding survival outcomes were retrieved. The association between the survival outcomes and the interval between conventional IRI and nal-IRI was analyzed. Results: Forty-one patients met the inclusion criteria. One patient (2.4%) had a partial response (PR), and 12 patients (29.3%) had stable disease (SD) as their best response. The median overall duration of nal-IRI treatment was 2.2 (IQR: 1.4 – 5.2) months. The median progression-free survival (mPFS) was 1.9 (95% confidence interval [CI] 1.7 – 2.0) months, while the 6-month PFS rate was 24.4%. The median overall survival (mOS) was 5.9 (95% CI 3.5 – 8.2) months, and the 6-month OS rate was 48.7%. The median interval between the discontinuation of conventional IRI and starting nal-IRI was 6.5 (3.4 – 13.2) months. An interval between conventional IRI and nal-IRI ≥6.5 months was significantly associated with prolonged OS (8.5 [95% CI 5.9 - 11.1] versus 4.3 [95% CI 2.7 – 5.9] months; p = 0.017), but comparable PFS (2.0 [95% CI 1.0 – 2.8] versus 1.7 [95% CI 1.5 – 1.9] months; p = 0.052). Conclusions: Patients previously treated with conventional IRI containing regimens appear to still benefit from nal-IRI plus 5-FU-LV. A longer interval between conventional IRI and nal-IRI was associated with better OS. A sequence strategy introducing a nal-IRI-based regimen at later lines may be feasible in selected APC patients previously treated with conventional IRI, given the limited therapeutic options. Further prospective studies are warranted.

PD: progressive disease.