A phase II study of nab-paclitaxel and gemcitabine as first line therapy in patients with cholangiocarcinoma ineligible for cisplatin-based chemotherapy (NACHO)

Introduction: Gemcitabine and cisplatin is the standard 1st line systemic treatment in patients with advanced cholangiocarcinoma (CCA). However, a substantial number of patients do not qualify for cisplatin due to comorbidities or poor performance status. The phase II pilot study NACHO evaluated the efficacy of nab-paclitaxel (125mg/m(2)) and gemcitabine (1000mg/m(2)) given on days 1,8 and 15 every 4 weeks as 1st line therapy in patients with advanced CCA ineligible for cisplatin-based chemotherapy. Methods: Patients with any comorbidity precluding cisplatin therapy, such as renal impairment, impaired hearing, increased risk or history for thromboembolic events, intolerance of extensive hydration, or significant cardiovascular disease were eligible. Primary endpoint was overall response rate (ORR) per RECIST 1.1. Secondary endpoints were progression-free survival (PFS), overall survival (OS), safety and patient reported outcome. Results: From 12/2016 to 07/2017 ten patients were prospectively enrolled and treated. The ORR with nab-paclitaxel/gemcitabine was 50%, the disease control rate (DCR) was 90%. Median PFS was 5.7 months (95% CI 5.3-6.1), and median OS was 7.8 months (95% CI 5.4-10.2). In total, 13 SAEs were documented without any new safety signals. There were 14 grade 3-4 treatment related adverse events (TRAEs) in 10 patients of the ITT population. Exploratory subgroup analyses including known prognostic markers were performed. Conclusions: The NACHO trial supports safety and efficacy of nab-paclitaxel and gemcitabine in patients with advanced CCA ineligible for cisplatin-based therapy and should be further evaluated in a larger prospective trial. Clinical trial information: EudraCT-No.: 2014-004981-52