Based on the results of the multicenter phase III NEXT trial published by Jeong et al in JAMA Network Open, the addition of a polymeric micellar paclitaxel to standard chemotherapy with gemcitabine plus cisplatin did not improve overall survival in patients with previously untreated advanced biliary tract cancer.
“Limited prospective data exist on the role of adding taxane to standard chemotherapy in the first-line treatment of advanced biliary tract cancers, especially in the Asian population, where biliary tract cancers are most prevalent,” the investigators commented. “This study provides further evidence regarding the limitations of intensified chemotherapy with the addition of taxanes in advanced biliary tract cancer.”
Study Details
A total of 150 patients (median [range] age = 65 [41–79] years; male: n = 87 [58%]) from seven tertiary institutions in South Korea were randomly assigned to receive first-line gemcitabine plus cisplatin with (n = 74) or without (n = 76) a polyethoxylated castor oil–free polymeric micelle formulation of paclitaxel. All were diagnosed with locally advanced unresectable, recurrent, or metastatic bile duct adenocarcinoma; were aged 19 to 79 years; had an Eastern Cooperative Oncology Group performance status score of 0 to 2; and had measurable or evaluable lesions.
This investigator-initiated study was prematurely terminated because of slow patient accrual. Follow-up data were provided for a median of 10.4 months (interquartile range = 6.5–16.7 months).
The investigators identified overall survival as the primary endpoint. Investigator-assessed and blinded independent central review–assessed progression-free survival, objective response rate, and safety were evaluated as secondary endpoints.
Key Findings
The median durations of overall survival were 12.0 (95% confidence interval [CI] = 9.9–15.8 months) and 11.1 (95% CI = 9.7–13.5 months) months with and without polymeric micellar paclitaxel, respectively (hazard ratio = 0.94, 95% CI = 0.63–1.41; P = .76). Progression-free survival, as assessed by both blinded independent central review and investigators, and the objective response rate were not found to significantly differ between the groups. According to the investigators, there were no unanticipated safety signals.
“To our knowledge, NEXT is the first phase III randomized clinical trial designed to evaluate the novel triplet combination of gemcitabine and cisplatin plus polymeric micellar paclitaxel, a polyethoxylated castor oil–free polymeric micelle formulation of paclitaxel, compared with gemcitabine and cisplatin alone,” the investigators concluded. “The study was terminated prematurely due to slow patient accrual, with approximately 70% of the planned participants enrolled. Our study did not meet its primary endpoint, because the addition of polymeric micellar paclitaxel did not improve overall survival compared with gemcitabine and cisplatin in patients with previously untreated advanced biliary tract cancer. Progression-free survival and response rates also did not show improvement with the inclusion of polymeric micellar paclitaxel. Both treatment regimens were well tolerated, with no unexpected safety signals reported.”
Kyu-pyo Kim, MD, PhD, of Asan Medical Center, University of Ulsan College of Medicine, Seoul, is the corresponding author of the article in JAMA Network Open.
Disclosure: The study was funded by Samyang Corp. For full disclosures of the study authors, visit jamanetwork.com.
