First-Line Nab-Paclitaxel and Gemcitabine in Advanced Cholangiocarcinoma
In a phase II trial reported in JAMA Oncology, Sahai et al found that the first-line combination of nab-paclitaxel and gemcitabine—though it did not meet the progression-free survival primary endpoint—may constitute a treatment option in advanced cholangiocarcinoma.
Study Details
In the study, 74 patients with untreated advanced or metastatic disease were enrolled at 23 sites in the United States and Europe between September 2014 and March 2016. Patients had a Child-Pugh score < 8; previous surgery, radiation, or liver-directed therapies were permitted. Patients received nab-paclitaxel at 125 mg/m2 followed by gemcitabine at 1,000 mg/m2 on days 1, 8, and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity. The primary outcome measure was an improved 6-month progression-free survival rate of 70% (null and alternative hypotheses of 55% and 70%) based on historical data and previous data on gemcitabine-platinum treatment.
Treatment Outcome
Patients received a median of 6 treatment cycles (range = 1–18), and the median follow-up was 10.2 months (range = 0.6–27.3 months). Progression-free survival at 6 months was 61%, which failed to meet the study objective. Median progression-free survival was 7.7 months, median time to disease progression was 7.7 months, and median overall survival was 12.4 months. The overall response rate was 30%, and the disease control rate was 66%. Declines in serum carbohydrate antigen 19-9 by < 50% were associated with nonsignificantly poorer median progression-free survival (hazard ratio [HR] = 2.02, P = .10) and overall survival (HR = 1.54, P = .34).
Adverse Events
The most common treatment-related adverse events of any grade were fatigue (70%), neutropenia (68%), and peripheral neuropathy (55%). Treatment-related grade ≥ 3 adverse events occurred in 82%, with the most common including neutropenia (43%), thrombocytopenia (16%), anemia (15%), fatigue (14%), leukopenia (10%), and elevated alkaline phosphatase level (10%).
The investigators concluded, “Although the trial did not meet its primary efficacy endpoint, the results indicate that a nab-paclitaxel plus gemcitabine regimen was well tolerated and may be an alternative option to current therapeutic approaches for advanced cholangiocarcinoma.”
The study was funded by Celgene Corporation.
Vaibhav Sahai, MBBS, MS, of the University of Michigan, Ann Arbor, is the corresponding author of the JAMA Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
