As reported in the Journal of Clinical Oncology by Shroff et al, the phase III SWOG S1815 trial showed that nab-paclitaxel plus gemcitabine/cisplatin (GAP regimen) did not significantly improve overall survival vs gemcitabine/cisplatin alone in newly diagnosed patients with advanced biliary tract cancers.
Study Details
In the U.S. multicenter open-label trial, 441 eligible patients were randomly assigned 2:1 between December 2018 and February 2021 to receive GAP (n = 294) or gemcitabine/cisplatin (n = 147). GAP consisted of gemcitabine at 800 mg/m2, cisplatin at 25 mg/m2, and nab-paclitaxel at 100 mg/m2 on days 1 and 8 of 21-day cycles; Gemcitabine/cisplatin consisted of gemcitabine at 1,000 mg/m2 and cisplatin at 25 mg/m2 on days 1 and 8 of 21-day cycles. For the GAP and gemcitabine/cisplatin groups, 26% and 28% had unresectable locally advanced disease, and 74% and 72% had metastatic disease. Among all patients, 67% had intrahepatic cholangiocarcinoma, 16% had gallbladder carcinoma, and 17% had extrahepatic cholangiocarcinoma. The primary outcome measure was overall survival.
Key Findings
Median overall survival was 14.0 months (95% confidence interval [CI] = 12.4–16.1 months) in the GAP group vs 13.6 months (95% CI = 9.7–16.6 months) in the gemcitabine/cisplatin group (hazard ratio [HR] = 0.91, 95% CI = 0.72–1.14, P = .41). Median progression free survival was 7.5 months (95% CI = 6.4–8.5 months) in the GAP group vs 6.3 months (95% CI = 4.4–8.2 months) in the gemcitabine/cisplatin group (HR = 0.89, 95% CI = 0.71–1.12, P = .32).
In exploratory subset analyses, the GAP group showed greater numeric benefit in overall survival and progression-free survival vs the gemcitabine/cisplatin group in locally advanced disease compared with metastatic disease; the differences were not significant (interaction P = .14 for overall survival and P = .17 for progression-free survival). Greater improvement in progression-free survival was observed for GAP vs gemcitabine/cisplatin among patients with gallbladder cancer vs intrahepatic cholangiocarcinoma or extrahepatic cholangiocarcinoma (P for interaction = .01), with no advantage in overall survival observed (P = .28.)
Grade ≥ 3 treatment-related hematologic adverse events were more frequent in the GAP group vs the gemcitabine/cisplatin group (60% vs 45%, P = .003). Grade 3 to 4 treatment-related nonhematologic adverse events that were more common in the GAP group included alanine aminotransferase increase, anorexia, constipation, diarrhea, edema, fatigue, hypomagnesemia, nausea, sepsis, sensory peripheral neuropathy, and vomiting. A total of seven deaths were considered treatment-related in the GAP group (from sepsis in three patients and cardiac arrest, superior vena cava syndrome, thromboembolic event, and upper gastrointestinal hemorrhage in one each); one death in the gemcitabine/cisplatin group was considered related to treatment.
The investigators concluded: “The addition of a taxane in the GAP regimen to the standard gemcitabine/cisplatin regimen did not improve [overall survival] in newly diagnosed [biliary tract cancer]. More toxicity was encountered with GAP versus [gemcitabine/cisplatin].”
Rachna T. Shroff, MD, MS, FASCO, of the University of Arizona Cancer Center, Tucson, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by National Cancer Institute grants and by Celgene Corporation (subsidiary of Bristol Myers Squibb). For full disclosures of all study authors, visit the Journal of Clinical Oncology.
