Benefit of second-line systemic chemotherapy for advanced biliary tract cancer: A propensity score analysis

Abstract

Whether 2 nd -line-chemotherapy (2LCTX) + best-supportive-care (BSC) benefits patients with advanced biliary tract cancer (aBTC) more than BSC alone is unclear. We therefore conducted a propensity-score-based comparative effectiveness analysis of overall survival (OS) outcomes in 80 patients with metastatic, recurrent, or inoperable aBTC, of whom 38 (48%) were treated with BSC + 2LCTX and 42 (52%) with BSC alone. After a median follow-up of 14.8 months and 49 deaths, the crude 6-, 12-, and 18-month Kaplan-Meier OS estimates were 77%, 53% and 23% in the BSC + 2LCTX group, and 29%, 21%, and 14% in patients in the BSC group (p = 0.0003; Hazard ratio (HR) = 0.36, 95%CI:0.20–0.64, p = 0.001). An inverse-probability-of-treatment-weighted (IPTW) analysis was conducted to rigorously account for the higher prevalence of favorable prognostic variables in the 2LCTX + BSC group. After IPTW-weighting, the favorable association between 2LCTX and OS prevailed (adjusted HR = 0.40, 95%CI: 0.17–0.95, p = 0.037). IPTW-weighted 6-, 12-, and 18-month OS estimates were 77%, 58% and 33% in the BSC + 2LCTX group, and 39%, 28% and 22% in the BSC group (p = 0.037). Moreover, the benefit of 2LCTX was consistent across several clinically-relevant subgroups. Within the limitations of an observational study, these findings support the concept that 2LCTX + BSC is associated with an OS benefit over BSC alone in aBTC.

Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm

“…Approximately 15–25% of patients are fit enough to receive second-line therapy [ 13 , 14 , 15 ]. Several retrospective studies [ 13 , 14 , 15 ] and a randomized phase III study (ABC-06) [ 16 ] have suggested a benefit of second-line chemotherapy following progression on cisplatin and gemcitabine.…”

“…Approximately 15–25% of patients are fit enough to receive second-line therapy [ 13 , 14 , 15 ]. Several retrospective studies [ 13 , 14 , 15 ] and a randomized phase III study (ABC-06) [ 16 ] have suggested a benefit of second-line chemotherapy following progression on cisplatin and gemcitabine. The standard second-line therapies include FOLFOX (5-FU, leucovorin, and oxaliplatin) [ 16 ], capecitabine plus irinotecan (XELIRI) [ 17 ], irinotecan monotherapy [ 17 ], and fluoropyrimidine (with 5-FU) monotherapy [ 13 ].…”

Long Non-Coding RNAs in Biliary Tract Cancer—An Up-to-Date Review

“…The common treatment for advanced BTC includes palliative treatment, radiation therapy and chemotherapeutic treatment using a combination regimen of cisplatin and gemcitabine, resulting in a median survival of only about one year [12][13][14]. Second line therapeutic options are not standardized and only show weak or moderate improvement in survival rates [15]. The lack of efficient therapeutic options and the high mortality rates demand for a better understanding of the underlying molecular mechanisms of BTC development and progression [16].…”

Phase II Trial of Trifluridine/Tipiracil in Patients with Advanced, Refractory Biliary Tract Carcinoma

“…Benefit with second-line chemotherapy following progression on cisplatin plus gemcitabine has been suggested in a number of retrospective studies [2,[9][10][11][12] [10]. The recently reported phase III, multicenter study ABC-06 [13] randomized patients with locally advanced and metastatic BTC following progression on cisplatin and gemcitabine to active symptom control (ASC) alone or ASC plus modified FOLFOX (mFOLFOX).…”

“…A number of retrospective studies have suggested a benefit from systemic chemotherapy following progression on first-line chemotherapy [2,[9][10][11][12]. A randomized, phase III study (ABC-06) reported improvement of median OS in patients who were refractory to first-line cisplatin and gemcitabine and treated with modified FOLFOX plus best supportive care over best supportive care alone [13].…”