A prospective, multicenter, phase II trial of albumin-paclitaxel plus cisplatin versus gemcitabine plus cisplatin in first-line treatment of advanced biliary tract tumors.

Abstract

4099 Background: The prognosis of biliary system tumors is poor, Gemcitabine combined with cisplatin has been the standard first-line treatment for advanced biliary system tumors, but its efficacy and adverse effects are unsatisfactory. Albumin-paclitaxel is a novel paclitaxel with a broad-spectrum anti-tumor effect, which has been widely used in the treatment of digestive system malignant tumors. Therefore, we designed this study to investigate the efficacy and safety of the combination of albumin-paclitaxel and cisplatin compared with gemcitabine combined with cisplatin in patients with previously untreated advanced biliary tract tumors. Methods: This is a multicenter, randomized, controlled, investigator-initiated Phase II trial designed to enroll patients with unresectable, recurrent, or metastatic cholangiocarcinoma (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder carcinoma). After enrollment, patients were randomly assigned to the experimental TP group (albumin paclitaxel 125mg/m2 iv, D1, 8 cisplatin 75mg/m2 IV, D1 Q21 ) or the control GP group (gemcitabine 1000mg/m2 IV, D1, 8 cisplatin 75mg/m2 iv, D1 Q21) and received six cycles of chemotherapy. The primary endpoint was PFS, and the secondary endpoint was OS, ORR, and safety. Results: Up to January 2022, 67 patients were enrolled, the 41male and 26 female patients had a median age of 55(range 32-74) years. Of the 67 enrolled patients, 33 were randomly assigned to the TP group and 34 to the GP group. Among the these patients, 47 were diagnosed with intrahepatic cholangiocarcinoma, 7 with extrahepatic cholangiocarcinoma, and 13 with gallbladder cancer. 48 patients had completed at least 2 cycles of chemotherapy and were available for evaluation, mPFS in the TP and the GP groups was 7.7 and 7.5 months, respectively (HR 1.33, CI 0.61 - 2.91,P = 0.469), mOS in TP and GP groups was 12.1 months and 12.9 months, respectively (HR 1.62, 95% CI 0.67-4.17,P = 0.271). After the first assessment, the ORR was 39.4% and 35.3% in the TP group and the GP group, respectively. In terms of side effects, bone marrow suppression (61% vs 76%) was the most predominant adverse events in both groups, abnormal liver and kidney function (56% vs 67%), gastrointestinal reactions (including nausea, vomiting, diarrhea, constipation, etc.) (46% vs 43%), rash or allergy (44% vs 37%), and other side effects such as fever and influenza symptoms (21% vs 24%) were also observed in the TP group and the GP group. Conclusions: The result of this study showed that the regimen of albumin paclitaxel combined with cisplatin was non-inferior to gemcitabine combined with cisplatin in terms of PFS, OS and ORR, and the safety advantages of the combination of albumin paclitaxel and cisplatin make it a potential regiment for first-line treatment of advanced biliary tract tumors. Clinical trial information: ChiECRCT-20180167.