Efficacy profile of nanoliposomal irinotecan + fluorouracil and leucovorin (nal-IRI+5-FU/LV) in gemcitabine-refractory metastatic pancreatic adenocarcinoma in elderly North American patients: A real-word experience.

Abstract

e16382 Background: Second-line treatment options for metastatic pancreatic adenocarcinoma (mPDAC) remain limited. The NAPOLI-1 trial showed improved outcomes with nanoliposomal irinotecan (nal-IRI) + 5-fluorouracil and leucovorin (5-FU/LV) compared to standard therapy. However, only a small proportion of the enrolled patients who received nal-IRI+5-FU/LV were North American (19/417), many under the age of 65, raising concerns regarding the generalizability of results to this population. This study aimed to evaluate the real-world effectiveness of nal-IRI + 5-FU/LV in a mostly elderly North American population with gemcitabine-refractory mPDAC. Methods: This was a retrospective cohort study performed in a single cancer center in South Florida serving a predominantly elderly population. Medical records of patients with mPDAC who had received combination of nal-IRI+5-FU/LV after progression on gemcitabine-based therapy for mPDAC from October 1, 2015 to January 31, 2023 were analyzed. The primary outcome was overall mean survival (OS), defined as time from from initiation of nal-IRI+5-FU/LV to date of death or last known alive. Secondary outcomes included progression free survival (PFS), and CA 19-9 response. Survival outcomes were analyzed using Kaplan-Meier methods and compared using the log-rank test. Cox proportional hazards regression was performed to estimate hazard ratios (HR) and assess the impact of clinical and demographic factors on the survival outcomes. A p -value < 0.05 was considered statistically significant. Results: A total of 68 patients were included; 79.4% (54) were > 65 years old. Median OS was 5.7 months (CI: 4.5-6.7), and median PFS was 2.3 months (CI: 1.8-2.8) compared to 6.2 and 3.1 months, respectively in NAPOLI-1. CA 19-9 response was obtained in 70.3% of patients compared to 68% in NAPOLI-1. On cox proportional hazards model, when adjusted for clinical and demographic factors, age > 65 years (HR = 5.383, p < 0.0098), and anemia (HR = 13.161, p = 0.009) were independently associated with increased mortality. Conclusions: In this real-world cohort of predominantly elderly North American patients with gemcitabine-refractory mPDAC, nal-IRI + 5-FU/LV demonstrated clinically meaningful effectiveness in OS and PFS comparable to those reported in the NAPOLI-1 trial. These findings support nal-IRI + 5FU/LV therapy as a viable second-line treatment option for the underrepresented elderly North-American population that is routinely encountered in clinical practice. Advanced age and anemia at baseline were identified as independent predictors of mortality, highlighting the importance of patient selection and risk stratification.