BACKGROUND & AIMS: Liposomal irinotecan (nal-IRI) combined with fluorouracil (5-FU)/leucovorin (LV) as a second-line treatment for biliary tract cancer (BTC) following progression on gemcitabine-based therapy yielded conflicting outcomes in the Korean NIFTY and German NALIRICC trials. This necessitated a comprehensive pooled analysis to evaluate its efficacy and safety.

METHODS: Individual patient data were pooled from the intention-to-treat populations of the NIFTY and NALIRICC trials. The primary endpoint was progression-free survival (PFS).

RESULTS: A total of 278 patients were included: 137 in the nal-IRI plus 5-FU/LV group and 141 in the 5-FU/LV group. The nal-IRI plus 5-FU/LV group showed significantly longer median PFS (3.6 months [95% CI 2.7-4.4] vs. 1.8 months [95% CI 1.5-2.6]; hazard ratio 0.65, p <0.001). Median overall survival was 8.1 months (95% CI 6.0-8.9) and 6.1 months (95% CI 5.3-7.5), respectively (hazard ratio 0.77, p = 0.051). Objective response rates were also higher in the nal-IRI plus 5-FU/LV group than in the 5-FU/LV group (17.5% vs. 2.8%; p <0.001). Post-study irinotecan-containing therapy was administered in 4 (2.9%) and 21 (15.3%) patients in the nal-IRI plus 5-FU/LV group and 5-FU/LV group, respectively. Adverse events varied by ethnicity, with gastrointestinal toxicities more common in Germans and neutropenia more prevalent in Koreans; treatment discontinuation without disease progression occurred in 31.3% vs. 8.0%, respectively.

CONCLUSION: The addition of nal-IRI to 5-FU/LV significantly improved PFS and objective response rates, supporting its potential as subsequent-line therapy. Differences in safety profiles underscore the relevance of ethnicity for nal-IRI in patients with BTC.

IMPACT AND IMPLICATIONS: Current standard of care for second-line therapy in patients with advanced biliary tract cancer (BTC) is FOLFOX. This study provides robust evidence supporting the potential role of adding liposomal irinotecan (nal-IRI) to fluorouracil and leucovorin (5-FU/LV) as a subsequent therapy for patients with BTC who have progressed on gemcitabine-based regimens. The findings demonstrate significant improvements in progression-free survival and objective response rates in a patient population for whom treatment options are limited. Furthermore, the study underscores the necessity of considering ethnic differences in adverse event profiles to optimize treatment administration and patient outcomes.

CLINICAL TRIAL REGISTRATION NUMBER: NCT03524508 and NCT03043547.