Advanced biliary tract cancer: clinical outcomes with ABC-02 regimen and analysis of prognostic factors in a tertiary care center in the United States

Abstract

Background: Gemcitabine plus cisplatin (GC) is currently the standard regimen for advanced biliary tract cancers (BTC) based on the outcomes in ABC-02 trial. Multiple factors can affect outcomes in these patients. This retrospective review evaluates the University of Cincinnati experience with GC in advanced intrahepatic (IHC)/ extrahepatic cholangiocarcinoma (EHC) and gall bladder carcinoma (GBC). Methods: In this study approved by University of Cincinnati IRB, retrospective analysis of advanced BTC patients seen between 01/2008 and 01/2015 was done. Kaplan Meyer method was used to calculate progression free survival (PFS), and overall survival (OS). Cox model was used to test the association between baseline variables and OS/PFS, adjusting for gender and age at diagnosis. Patients were identified using ICD code for BT tumors, 26 patients met inclusion criteria: histologically proven advanced BTC that received GC as their initial chemotherapy. GC was given as per ABC-02 protocol with appropriate modifications until disease progression or unacceptable toxicities. Results: Median age at diagnosis was 62 years (range, 31-81 years). Eighteen (69%) were IHC, 5 EHC, 3 GBC, 61% male, 73% whites. Performance status (PS): 0-1: 69%, PS 2: 31%. Baseline CA19-9 data was available for 21 patients, (range 1 to 69,543), and abnormal CA19-9 was seen in 14 patients (54%). PFS was 4.5 months (95% CI: 3.1-8.9 months) and OS was 10.5 months (95 % CI: 7.9-18.8 months). OS at 6 and 12 months was 69% (18/26) and 42% (11/26). Thirty-eight percent (10/26) received 2nd line chemotherapy, of these 9/10 received 5FU based chemotherapy. Eleven percent (3/26) received 3rd line chemotherapy. Increase in baseline carcinoembryonic antigen (CEA), alanine aminotransferase, alkaline phosphatase (ALP) and total bilirubin was associated with increased risk of death while increase in baseline CEA and ALP was associated with increased risk of progression (P valve <0.05). In the group of patients who had all three major risk factors (PS ≥2, CEA >3, and stage IVb), the median survival was 2.9 months (95% CI: 2.6-9.3 months), which was significantly worse compared to rest of the population [median 18 months (95% CI: 5.4-19.5 months), P<0.01]. Conclusions: Our data supports the use of GC as a first line regimen for advance BTC in a non-clinical trial setting. Results are comparable to those reported in ABC-02 trial, despite inclusion of PS 2 patients whom constituted 31% of our population. In the patient population studied, baseline CEA and liver function test appeared able to predict response to GC in advanced BTC. Patients with all three high risk factors (PS ≥2, CEA >3, and stage IVb) did poorly and may need careful selection prior to initiating chemotherapy.

Translating the ABC-02 trial into daily practice: outcome of palliative treatment in patients with unresectable biliary tract cancer treated with gemcitabine and cisplatin

“…In contrast with a recent similar retrospective analysis in 26 metastatic BTC patients [14], we observed a difference in OS in patients treated with gemcitabine and cisplatin in daily practice compared with patients in the ABC-02 trial. Almost half of these patients [14] (49%) received second or third line chemotherapy, which may explain the higher OS in the other retrospective analysis (9.5 vs. 10.5 months).…”

Predictive factors of the treatment outcome in patients with advanced biliary tract cancer receiving gemcitabine plus cisplatin as first-line chemotherapy

“…Although PS is a somewhat subjective and vague assessment of the physical condition of cancer patients, it was identified as the most important predictor of the survival in advanced BTC patients receiving chemotherapy. Indeed, some previous studies have also reported PS as a prognostic factor in patients with advanced BTC, in conformity with our findings [8–11, 13, 14, 16–21]. Although previous reports suggest a poor prognosis in patients with PS 2 [8, 10, 11, 17, 18, 21], both patients with PS 2 and PS 1 had a poor prognosis in this study.…”

Circulating levels of soluble urokinase plasminogen activator receptor predict outcome after resection of biliary tract cancer

“…1,3 If surgical tumor resection is not feasible, chemotherapy with gemcitabine and cisplatin represents the standard of care, resulting in a median overall survival (OS) of 10-12 months. [4][5][6] Importantly, the postoperative outcome following BTC resection is very heterogeneous and the majority of successfully resected patients (R 0 resection) face disease recurrence, 7 resulting in an overall 5-year survival rate of less than 30%. [8][9][10] Moreover, while current data suggest a benefit of more aggressive adjuvant treatment regimens in pancreatic cancer, which shares many clinicopathological similarities with BTC, 11 data from lager clinical trials evaluating this concept in patients with BTC are still missing (NCT02170090).…”