The impact of second-line treatment after fist-line cisplatin plus gemcitabine in advanced biliary tract cancers: A mono-institutional retrospective study.

Abstract

e16180 Background: The prognosis of advanced biliary tract cancers (ABTCs) is poor with a 5 year overall survival (OS) lower than 20%. The standard of care first-line chemotherapy is the combination of cisplatin plus gemcitabine. The efficacy of second-line treatment is supported by few evidence and only one randomized phase III clinical trial is reported. The ABC-06 trial showed a minimal improvement in overall survival with FOLFOX compared to active symptoms control (ASC). Herein, we provide a retrospective analysis of patients treated with second-line treatment at our Institution investigating the impact of treatment regimen and possible prognostic or predictive factors. Methods: ABTCs patients receiving second-line treatment following a first-line chemotherapy with cisplatin plus gemcitabine were included in the analysis. The following variables were collected: gender; age (< 65 years vs ≥ 65 years); baseline ECOG PS (0-1 vs ≥2); second-line regimen (FOLFIRI vs FOLFOX); comorbidities (yes vs no); number of comorbidities (0-1 vs ≥ 2); number of metastatic sites (1 vs ≥2). Univariate and multivariate analysis for progression free survival (PFS) and OS were performed. Results: Fifty-one patients affected with ABTCs receiving second-line treatment between January 2016 and May 2021 were included in the analysis. The median age was 70 years (38-82), 39% (20) were males, 70% (36) were aged ≥ 65 years, ECOG PS was 0-1 in 86% (44) of patients; 39% (20) had ≥2 comorbidities; 60% (31) had ≥ 2 metastatic sites. Second-line regimen included FOLFIRI (28; 55%), FOLFOX (15; 29%), capecitabine (2; 4%) and experimental drugs (6; 12%). The overall population median PFS and OS at second-line were 3.5 months (median follow-up 11.4 months) and 8.8 months (median follow-up 22.6 months), respectively. Two patients (4%) achieved a partial response and the disease control rate was 39%. At the univariate and multivariate analysis, no variable was associated with PFS. At the univariate analysis, second-line regimen FOLFIRI (p = 0.03) and single metastatic site (p = 0.06) were associated with improved OS; at the multivariate analysis only the second-line regimen was confirmed associated with OS (p = 0.02). In particular, out of 43 evaluable patients, the median OS according to treatment (FOLFIRI vs FOLFOX) was 11.3 months versus 5.4 months (p = 0.019, HR 0.46, 95% CI: 0.18-0.88). Conclusions: Despite the retrospective analysis and the limited sample size, we confirm the importance of second-line chemotherapy in ABTCs patients, when feasible. Our results show that the second-line FOLFIRI regimen after a platinum-containing fist-line, was independently associated with improved OS. Given that the ABC-06 trial compared FOLFOX to ASC, a randomized trial of FOLFOX vs FOLFIRI as second-line would provide further information in this setting.