103P - Individual patient data (IPD) meta-analysis of randomised trials to compare efficacy of second-line fluoropyrimidine-based chemotherapy in advanced biliary tract cancer (BTC)

Background

For patients (pts) with advanced BTC with progression on gemcitabine plus cisplatin (GemCis), fluoropyrimidine-based chemotherapy, including liposomal irinotecan (nal-IRI) plus fluorouracil and leucovorin (5-FU/LV) and 5-FU/LV plus oxaliplatin (FOLFOX) showed clinical benefit in prior randomized trials (NIFTY and ABC-06). However, there is no trial for head-to-head comparison among these agents.

Methods

We performed IPD meta-analysis of two multicenter, randomized trials performed in South Korea, which compared efficacy of second-line chemotherapy for advanced BTC after progression on GemCis, including the phase 2b NIFTY trial (nal-IRI plus 5-FU/LV vs. 5-FU/LV, NCT03524508) and the phase 2 FIReFOX trial (modified FOLFOX [mFOLFOX] vs. modified 5-FU/LV plus irinotecan [mFOLFIRI], NCT03464968). ITT population of the two trials were included and survival outcomes were compared between the 4 treatment groups by pairwise log-rank test. Hazards ratio (HR) adjusted by potential prognostic variables was estimated by Cox proportional hazards modeling with shared frailty to account for the trials effect.

Results

A total of 278 pts were included in this analysis (178 pts from the NIFTY trial and 99 pts from the FIReFOX trial). The nal-IRI plus 5-FU/LV group (n=88) showed significantly better overall survival compared to the mFOLFOX group (n=49, p = 0.02), mFOLFIRI group (n=50, p = 0.03), and 5-FU/LV group (n=90, p = 0.008). Multivariable analysis showed consistent trends with adjusted HR of 1.44 (95% CI 0.93-2.07, p = 0.11), 1.36 (95% CI 0.92-2.03, p = 0.13), and 1.52 (95% CI 1.37-1.09-2.10, p = 0.01), respectively. Also, nal-IRI plus 5-FU/LV group showed trends toward better progression-free survival compared to the other 3 groups with adjusted HR of 1.44 (95% CI 0.98-2.11, p = 0.06), 1.29 (95% CI 0.87-1.89, p = 0.20), and 1.88 (1.38-2.55, p < 0.001), respectively.

Conclusions

Nal-IRI plus 5-FU/LV showed better survival outcomes when compared to mFOLFOX, mFOLFIRI, or 5-FU/LV alone. Nal-IRI plus 5-FU/LV may be a preferable second-line regimen for advanced BTC pts without targetable genetic alterations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Servier.

Disclosure

All authors have declared no conflicts of interest.