Gemcitabine and Cisplatin Plus Polymeric Micellar Paclitaxel and Survival in Advanced Biliary Tract Cancer: A Randomized Clinical Trial.

Importance: 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.

Objective: To assess the efficacy and safety of polyethoxylated castor oil-free polymeric micelle formulation of paclitaxel (hereafter, polymeric micellar paclitaxel), in combination with gemcitabine and cisplatin in patients with untreated advanced biliary tract cancers.

Design, setting, and participants: This open-label, phase 3 randomized clinical trial was conducted across 7 centers in South Korea from September 1, 2019, to October 31, 2022. Patients were eligible if they had previously untreated, locally advanced unresectable, recurrent, or metastatic adenocarcinoma of the bile duct, were aged 19 to 79 years, had an Eastern Cooperative Oncology Group Performance Status of 0 to 2, and had measurable or evaluable lesions according to Response Evaluation Criteria in Solid Tumorsversion 1.1.

Interventions: Patients were randomized to receive either polymeric micellar paclitaxel, 100 mg/m2; gemcitabine, 800 mg/m2; and cisplatin, 25 mg/m2; on days 1 and 8 or gemcitabine, 1000 mg/m2, and cisplatin, 25 mg/m2, on days 1 and 8 every 21 days. A total of 9 cycles were planned for both groups.

Main outcomes and measures: The primary end point was overall survival. Secondary end points included investigator-assessed and blinded independent central review-assessed progression-free survival, objective response rate, and safety.

Results: A total of 150 patients (median [range] age, 65 [41-79] years; 87 [58%] male) were randomly assigned to the study (74 in the gemcitabine and cisplatin combined with polymeric micellar paclitaxel group and 76 in the gemcitabine and cisplatin group). The study was prematurely terminated due to slow patient accrual. The median (IQR) follow-up duration was 10.4 (6.5-16.7) months. The median overall survival was 12.0 (95% CI, 9.9-15.8) months in the gemcitabine and cisplatin combined with polymeric micellar paclitaxel group and 11.1 (95% CI, 9.7-13.5) months in the gemcitabine and cisplatin group (hazard ratio, 0.94; 95% CI, 0.63-1.41; P = .76). Both blinded independent central review-assessed and investigator-assessed progression-free survival as well as the objective response rates did not differ significantly between the 2 groups. No unanticipated safety signals were observed.

Conclusions and relevance: In this randomized clinical trial, gemcitabine and cisplatin combined with polymeric micellar paclitaxel did not improve survival compared with gemcitabine and cisplatin combined in patients with previously untreated advanced biliary tract cancer. This study provides further evidence regarding the limitations of intensified chemotherapy with the addition of taxanes in advanced biliary tract cancer.

Trial registration: cris.nih.go.kr identifier: KCT0003726.