Efficacy of fluoropyrimidine-based chemotherapy in patients with advanced biliary cancer after failure of gemcitabine plus cisplatin: Retrospective analysis of 321 patients.

Abstract

425 Background: In advanced biliary tract cancer (BTC), the role of 2nd line chemotherapy after failure of 1st line gemcitabine plus cisplatin (GEMCIS) has not been established. Fluoropyrimidine(FP)-based regimens are widely used as 2nd line treatment in clinical practice. We retrospectively analyzed the efficacy of 2nd line FP-based chemotherapy in patients(pts) with advanced BTC after failure of GEMCIS. Methods: Histologically confirmed advanced BTC pts who received 1st line GEMCIS at Asan Medical Center between December 2010 and June 2016 were identified. Among 748 pts treated with GEMCIS, 331 patients (44%) subsequently received 2nd line chemotherapy and FP-based regimens were used in 321 pts (97%). Results: The median age was 60 years (range, 27-82) and 57% of pts were male. Intrahepatic cholangiocarcinoma(IH-CCC) (44%) was the most common type, and followed by extrahepatic cholangiocarcinoma (32%). Most pts (n = 289, 89%) had metastatic/recurrent disease at the time of 1st line treatment. FP alone and FP plus platinum combination were used in 255 pts (79%) and 66 pts (21%), respectively. In pts with measurable disease, response rate (RR) was 3% (8/301) and disease control rate was 47% (142/301). After a median follow-up of 27.6 months (0.9-70.4 months), the median progression free survival (PFS) and overall survival (OS) were 1.9 months (95% CI, 1.6-2.2) and 6.5 months (95% CI, 5.9-7.0). RR was significantly higher in pts with combination of FP and platinum compared to FP alone (8% vs 1%, p = 0.009). However, there were no statistically significant differences in terms of PFS (p = 0.43) or OS (p = 0.88) between two groups. In the multivariate analysis for OS, IH-CCC, initially metastatic disease and elevated CA 19-9 level at the time of 1st line treatment, and time-to-progression at 1st line GEMCIS > 4 months were independent poor prognostic factors. Conclusions: In this analysis, FP-based regimen showed modest efficacy as 2nd line chemotherapy for advanced BTC patients after failure of 1st line GEMCIS. Combination of FP and platinum was not associated with improved survival outcomes compared to FP monotherapy, despite of higher RR.