Addition of Nab-Paclitaxel to Standard Gemcitabine and Cisplatin Did Not Significantly Improve Survival for Patients With Newly Diagnosed Biliary Tract Cancer

According to results from the phase 3 SWOG-S1815 study, the addition of nab-paclitaxel to gemcitabine plus cisplatin did not significantly improve survival outcomes among patients with newly diagnosed, unresectable locally advanced or metastatic biliary tract cancer. 

“The therapeutic landscape for [biliary tract cancer] has expanded significantly over recent years largely because of advances in molecularly targeted therapies and immunotherapies,” stated Rachna Shroff, MD, University of Arizona Cancer Center, Tucson, Arizona, and coauthors. “However, the survival benefit of adding immune checkpoint inhibitors to frontline gemcitabine and cisplatin chemotherapy for advanced disease is modest.” 

In this open-label study, researchers enrolled 441 patients with newly diagnosed, unresectable locally advanced or metastatic intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder carcinoma. Patients were randomized on a 2-to-1 basis to receive either 800 mg/m² of gemcitabine plus 25 mg/m² of cisplatin and 100 mg/m² of nab-paclitaxel on days 1 and 8 or 1,000 mg/m² of gemcitabine plus 25 mg/m² of cisplatin once daily on days 1 and 8 in 21-day cycles (control arm). The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS), objective response rate (ORR), disease control rate, and safety. 

At analysis, the median OS was 14 months in the experimental arm and 13.6 months in the control arm (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.72 to 1.14; P = .41). The median PFS was 7.5 months and 6.3 months, respectively (HR, 0.89; 95% CI, 0.71 to 1.12; P = .32). The ORR was 31% in the experimental arm and 21% in the control arm (P = .03). Disease control rates were 78% and 67%, respectively (P = .03). The most common grade 3/4 treatment-related adverse events occurring in ≥ 10% of patients included anemia, neutropenia, and thrombocytopenia. 

“Triplet chemotherapy should not routinely be offered to patients with advanced [biliary tract cancer],” concluded Journal of Clinical Oncology Associate Editor Andrew Ko, MD, University of California, San Francisco, California. 

“Acknowledging the heterogeneous biology of biliary malignancies, there is a need for rational genomic, transcriptomic, and artificial intelligence tools to not only select patients for targeted molecular and immune therapies, but also to guide targeted cytotoxic chemotherapies in future clinical trials,” concluded Dr Shroff et al. 

Source: 

Shroff RT, King G, Colby S, et al. SWOG S1815: A phase III randomized trial of gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin in newly diagnosed, advanced biliary tract cancers. Published online: December 13, 2024. doi: 10.1200/JCO-24-01383