Early-phase trials compared to first- and second-line FDA-approved treatments in patients with advanced gallbladder cancer and cholangiocarcinoma.

Abstract

e13020 Background: Patients with advanced cholangiocarcinoma (CC) and gallbladder carcinoma (GC) have few effective therapeutic options. We compared prognostic factors and clinical outcomes of CC/GC pts treated on phase I trials with that of their first-, second-line and last Food and Drug Administration (FDA)-approved therapy given in setting of metastatic disease. Methods: We retrospectively reviewed electronic medical records of patients with GC and CC evaluated in the phase I program clinic from November 2004 to March 2011. Results: Of the 72 patients with CC or GC, 32 (44%) were not enrolled on a trial mainly due to clinical deterioration (n=25). Of 40 treated patients (GC=6; CC=34; median age 60 years; median prior systemic therapies = 3), 8 (20%) had stable disease (SD) > 6 months; 3 (8%) achieved a partial response (PR); SD > 6 months/PR was observed mainly on protocols with hepatic arterial infusion drug administration and/or angiogenic inhibitors, anti-her2/neu agents or a novel MAPK/ERK kinase (MEK) inhibitor. Median progression-free survival (PFS) on phase I trials was 2.0 months (95% CI 1.7, 2.8) versus 3.0 months (95% CI 2.4, 5.0; p=0.95), 3.0 months (95% CI 2.3, 4.6; p=0.98), and 3.0 months (95% CI 2.4, 3.9; p=0.79) for their first-, second-, and last systemic therapy with FDA-approved agents given in the metastatic setting, respectively. In univariate analysis, factors associated with a shorter Phase I PFS were > 3 metastatic sites, elevated ALT (>56 IU/L), serum creatinine (>1.6mg/dL), and CA19-9 (>35U/mL). Conclusions: In heavily pretreated patients, PFS in the clinical trials setting remained poor but did not differ significantly from that of their first-line, second-line, and last prior therapy with FDA-approved agents. Response rate (SD >6 months/PR) of 28% was seen in trials with locoregional treatment or inhibitors of angiogenesis, her2/neu or MEK.