A recent phase 3 clinical trial, SWOG S1815, has found that adding nab-paclitaxel to the standard chemotherapy regimen of gemcitabine and cisplatin (GC) does not significantly improve overall survival in patients with newly diagnosed, advanced biliary tract cancer (BTC). The study, published in the Journal of Clinical Oncology, highlights the challenges in treating this heterogeneous malignancy.
The multicenter, open-label trial enrolled 441 patients with newly diagnosed locally advanced unresectable or metastatic BTC. Participants were randomized to receive either the GAP regimen (gemcitabine, cisplatin, and nab-paclitaxel) or GC alone. The primary endpoint was overall survival (OS).
Key Findings
The median overall survival was 14.0 months in the GAP group and 13.6 months in the GC group (HR = 0.91, 95% CI = 0.72-1.14, P = .41). Progression-free survival (PFS) was also similar between the two groups, with 7.5 months for GAP and 6.3 months for GC (HR = 0.89, 95% CI = 0.71-1.12, P = .32).
Exploratory subset analyses suggested potential benefits of the GAP regimen in patients with locally advanced disease and gallbladder carcinoma, but these differences were not statistically significant. Specifically, greater PFS improvement was observed for GAP vs GC among patients with gallbladder cancer vs intrahepatic cholangiocarcinoma or extrahepatic cholangiocarcinoma (P for interaction = .01), with no advantage in overall survival observed (P = .28.)
Toxicity Profile
The study also revealed a higher incidence of grade 3 or higher treatment-related adverse events in the GAP group (60%) compared to the GC group (45%, P = .003). These included hematologic toxicities such as anemia, neutropenia, and thrombocytopenia, as well as non-hematologic toxicities like increased alanine aminotransferase (ALT), anorexia, constipation, diarrhea, edema, fatigue, hypomagnesemia, nausea, sepsis, and sensory peripheral neuropathy. Seven treatment-related deaths occurred in the GAP group versus one in the GC group.
Implications for Treatment
The results suggest that the addition of nab-paclitaxel to gemcitabine and cisplatin does not provide a significant survival advantage for patients with advanced BTC and is associated with increased toxicity. According to the study authors, the heterogeneity of biliary malignancies contributes to the challenges in treating the disease.
Dr. Rachna T. Shroff, MD, MS, FASCO, of the University of Arizona Cancer Center, the corresponding author of the Journal of Clinical Oncology article, emphasized the need for future research to incorporate genomic, transcriptomic, and artificial intelligence tools to identify patients who may benefit most from specific therapies.
Study Details
- Trial: SWOG S1815 (NCT03768414)
- Phase: 3
- Design: Randomized, open-label
- Participants: 441 patients with newly diagnosed, advanced BTC
- Regimens:
- GAP: Gemcitabine 800 mg/m2, cisplatin 25 mg/m2, and nab-paclitaxel 100 mg/m2 on days 1 and 8 of a 21-day cycle
- GC: Gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle
- Primary Endpoint: Overall survival
