Real-world evidence on second line chemotherapy in advanced biliary tract carcinoma refractory to gemcitabine and oxaliplatin (GemOx)

BACKGROUND: Advanced biliary tract carcinoma (aBTC) comes with poor prognosis. Gemcitabine with oxaliplatin (GemOx) has emerged as a pragmatic alternative to gemcitabine with cisplatin and has been a preferred first line palliative option at many centres around the world. The evidence on second line chemotherapy following treatment failure of GemOx is scarce. METHODS: A retrospective multicentre cohort study in the Southeast healthcare region of Sweden, covering nine years (2011-2020) and three hospitals, was conducted. All patients with aBTC who had received first line GemOx and any second line treatment thereafter were included. Treatment patterns and clinicopathological prognostic parameters were explored. RESULTS: In a cohort of 121 patients with aBTC who had received GemOx in the first line setting, 57 (47%) had proceeded to any type of second line systemic therapy and were included in this study. The most used regimen was capecitabine single agent in 37 (64.9%) patients followed by intravenous 5-FU (9, 15.8%). Median overall survival (OS) in the total cohort was 4.1 months (95% CI 3.2-5.0). Six- and twelve-month survival rates were 35.6% and 18.6%. Median time to treatment failure (TTF) was 1.8 months (95% CI 1.5-2.2). Performance status (PS) 2, according to Eastern Cooperative Oncology Group (ECOG), was an independent predictor for poor OS and TTF. Progression free survival (PFS) of < 6 months during first line treatment and extrahepatic localisation were independent predictors for poor OS. A nomogram was established using ECOG PS, 1st line PFS and primary tumour site. An exploratory prognostic model showed that patients with high total score in the nomogram had OS of 2.9 months compared to 4.3 months in patients with intermediate score and 13.1 months in patients with low score. CONCLUSION: Patients with aBTC receiving second line chemotherapy following first line GemOx have very dismal prognosis. PS 0-1, first line PFS ≥ 6 months and intrahepatic disease localisation indicate better prognosis. These data highlight the need for improved and personalised treatment strategies in refractory aBTC.