Gemcitabine and Cisplatin +/- Nab-Paclitaxel for Newly Diagnosed BTC: Results From SWOG S1815

The phase 3 randomized SWOG S1815 trial has evaluated a combination of gemcitabine, nab-paclitaxel, and cisplatin (GAP) against gemcitabine and cisplatin alone (GC) in patients newly diagnosed with locally advanced unresectable or metastatic biliary tract cancer (BTC).

The study also included patients with intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder carcinoma (GBC). Each patient was randomly assigned 2:1 to receive either GAP (gemcitabine 800 mg/m2, cisplatin 25 mg/m2, and nab-paclitaxel 100 mg/m2 intravenously once per day on days 1 and 8 of a 21-day cycle) or GC (gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 intravenously once per day on days 1 and 8 of a 21-day cycle).

A total of 441 patients were eligible and analyzed for the study. ICC was present in 67% of patients, while 16% and 17% of patients had GBC and ECC, respectively. No significant difference was seen in overall survival (OS) in treatment with GAP versus GC.

The median OS of GAP was 14 months (95% CI, 12.4 to 16.1), and 13.6 months in patients who underwent GC (95% CI, 9.7 to 16.6); hazard ratio (HR), 0.91 (95% CI, 0.72 to 1.14); P=.41. The median progression-free survival (PFS) was similar between treatments, with a median PFS of 7.5 months for GAP (95% CI, 6.4 to 8.5) and 6.3 months for GC (95% CI, 4.4 to 8.2); HR, 0.89 (95% CI, 0.71 to 1.12); P=.32.

An exploratory subset analysis found that the OS and PFS benefits of GAP versus GC were greater in locally advanced disease compared with metastatic disease, but not statistically significant (interaction P=.14 for OS and P=.17 for PFS). GAP also showed greater improvement in PFS over GC in patients with GBC compared to those with ICC or ECC (interaction P=.01), but not OS (interaction P=.28).

Results of SWOG S1815 have shown that adding a taxane in the GAP regimen to the standard regimen of GC does not improve OS in patients with newly diagnosed BTC, and more toxicity is present when utilizing GAP over GC.