Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial
Open accessAbstract
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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The cisplatin/nab-paclitaxel/gemcitabine combination indicates enhanced efficacy and potential to mitigate resistance in advanced biliary tract cancer.
“indicating enhanced efficacy and potential to mitigate resistance.”
From Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies (2025) · cites this paper as [33]
The Abstract and Discussion report promising efficacy for the triplet in advanced biliary tract cancer, with survival outcomes favorable to historical gemcitabine–cisplatin controls. They do not show that the combination mitigates treatment resistance; the Discussion’s reference to a chemoresistant cancer concerns pancreatic cancer in a different study. (LLM, conf=0.87)
Experimental — accuracy not yet measuredCisplatin combined with nab-paclitaxel/gemcitabine improved clinical outcomes in patients with advanced biliary tract cancer, with median overall survival of 19.2 months and median progression-free survival of 11.8 months.
“For example, a study by Shroff et al. demonstrated that the combination of cisplatin with nab-paclitaxel/gemcitabine resulted in improved clinical outcomes, including mOS of 19.2 months and a mPFS of 11.8 months in patients with advanced BTC (NCT02392637) [33], indicating enhanced efficacy and potential to mitigate resistance.”
From Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies (2025) · cites this paper as [33]
Enhancing cisplatin-gemcitabine with nab-paclitaxel resulted in mOS improvements up to 19.2 months and high disease control rates (84%).
“Enhancing this regimen with nab-paclitaxel has resulted in mOS improvements up to 19.2 months and high disease control rates (84%) (NCT02392637) [33].”
From Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies (2025) · cites this paper as [33]
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- Authors
- Shroff, R. T., Javle, M. M., Xiao, L., Kaseb, A. O., Varadhachary, G. R., Wolff, R. A., Raghav, K. P. S., Iwasaki, M., Masci, P., Ramanathan, R. K., Ahn, D. H., Bekaii-Saab, T. S., & Borad, M. J.
- Affiliations
- University of Arizona Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Mayo Clinic (US)
- Department of Medical Oncology, Mayo Clinic, Phoenix, Arizona
- Corresponding author
- Shroff, Rachna T.
- ORCID
- Venue
- JAMA Oncology
- Publisher
- American Medical Association (AMA)
- Published
- 2019-06-01
- Volume
- 5
- Issue
- 6
- Pages
- 824
- ISSN
- 2374-2437 (ISSN-L)
- PMC
- PMC6567834
- OpenAlex
- W2937317161
- Cited by
- 468
- References
- 21
- Citations by year
- 2026: 27 · 2025: 52 · 2024: 61 · 2023: 82 · 2022: 94 · 2021: 91 · 2020: 46 · 2019: 14 · 2018: 1
- FWCI
- 58.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P30CA016672)
- Topics
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gallbladder and Bile Duct Disorders
- Keywords
- advanced biliary tract cancer, gemcitabine, cisplatin, nab-paclitaxel, cholangiocarcinoma, gallbladder cancer, progression-free survival, overall survival, metastatic disease, combination chemotherapy, dose reduction, hematologic adverse events, metastatic cholangiocarcinoma, metastatic gallbladder cancer
- MeSH terms
- Gemcitabine, Aged, Albumins, Antineoplastic Combined Chemotherapy Protocols, Bile Duct Neoplasms, Cisplatin, Deoxycytidine, Female, Humans, Male, Middle Aged, Treatment Outcome, Paclitaxel
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