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Original Investigation
April 18, 2019

Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial

Author Affiliations
  • 1Division of Hematology/Oncology, Department of Medicine, University of Arizona Cancer Center, Tucson
  • 2Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston
  • 3Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston
  • 4Department of Medical Oncology, Mayo Clinic, Phoenix, Arizona
JAMA Oncol. 2019;5(6):824-830. doi:10.1001/jamaoncol.2019.0270
Key Points

Question  Does the addition of nab-paclitaxel to gemcitabine-cisplatin therapy prolong progression-free survival among patients with advanced biliary tract cancers when compared with that for historical controls treated with gemcitabine-cisplatin alone?

Findings  In this phase 2 trial that included 60 patients, administration of nab-paclitaxel plus gemcitabine-cisplatin resulted in median progression-free survival of 11.8 months and median overall survival of 19.2 months in an intention-to-treat analysis. The partial response rate was 45%; the disease control rate was 84%.

Meaning  Administration of nab-paclitaxel plus gemcitabine-cisplatin may prolong survival vs administration of gemcitabine-cisplatin alone for the treatment of advanced biliary tract cancers.

Abstract

Importance  Administration of gemcitabine-cisplatin, the current standard therapy for advanced biliary tract cancers, results in median progression-free survival and overall survival of 8.0 and 11.7 months, respectively. New treatments offering improved survival outcomes are therefore needed.

Objective  To evaluate the association between progression-free survival and the addition of nanoparticle albumin-bound (nab)–paclitaxel to gemcitabine-cisplatin for the treatment of patients with advanced biliary tract cancer.

Design, Setting, and Participants  This open-label, single-arm, phase 2 clinical trial conducted at the University of Texas MD Anderson Cancer Center and the Mayo Clinic in Phoenix, Arizona, enrolled 62 patients with advanced biliary tract cancers between April 14, 2015, and April 24, 2017.

Interventions  Patients initially received gemcitabine, 1000 mg/m2, cisplatin, 25 mg/m2, and nab-paclitaxel, 125 mg/m2, on days 1 and 8 of 21-day cycles. Owing to hematologic adverse events among the first 32 patients enrolled, these starting doses were reduced to 800, 25, and 100 mg/m2, respectively, for the remaining 28 patients.

Main Outcomes and Measures  The primary trial end point was investigator-assessed progression-free survival in the intention-to-treat population.

Results  Of 60 patients who started treatment, the mean (SD) age was 58.4 (11.0) years, 38 (63%) had intrahepatic cholangiocarcinoma, 9 (15%) had extrahepatic cholangiocarcinoma, 13 (22%) had gallbladder cancer, 47 (78%) had metastatic disease, and 13 (22%) had locally advanced disease. Median follow-up was 12.2 (95% CI, 9.4-19.4) months, and median progression-free survival was 11.8 (95% CI, 6.0 to 15.6) months. The partial response rate was 45%, and the disease control rate was 84%. Median overall survival was 19.2 months (95% CI, 13.2 months to not estimable). Patients in the safety population (n = 57) received a median of 6 (interquartile range, 3-11) cycles of treatment; 26 patients (46%) remained on their starting dose throughout the trial. Grade 3 or higher adverse events occurred in 58% of patients, and 9 patients (16%) withdrew owing to adverse events. Neutropenia was the most common grade 3 or higher adverse event, occurring in 19 patients (33%) overall. Post hoc analyses showed that treatment efficacy was not significantly associated with starting dose, tumor type, or disease status and that tolerability was improved with reduced- vs high-dose treatment.

Conclusions and Relevance  Treatment with nab-paclitaxel plus gemcitabine-cisplatin prolonged median progression-free survival and overall survival vs those reported for historical controls treated with gemcitabine-cisplatin alone. These findings will be tested in a phase 3 randomized clinical trial.

Trial Registration  ClinicalTrials.gov identifier: NCT02392637

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