SWOG 1815, first-ever phase 3 trial in BTC, fails

The triplet regimen of nab-paclitaxel plus gemcitabine plus cisplatin (GCN) did not improve the health outcomes in untreated patients with advanced biliary tract cancer (BTC), the first-ever phase 3 trial in this population demonstrated.

A phase 2 study displayed encouraging anti-tumour activity of GCN in patients with advanced BTC, with a reported median overall survival (OS) of 19.2 months [1]. Following these results, Prof. Rachna Shroff (University of Arizona Cancer Center, AZ, USA) and co-investigators designed the first phase 3 trial in patients with untreated, advanced cholangiocarcinoma or gallbladder cancer (n=441) [2]. Patients were randomised 2:1 to gemcitabine, 800 mg/m², plus cisplatin, 25 mg/m², and nab-paclitaxel, 100 mg/m², intravenous administration at days 1 and 8 of a 21-day cycle, or to standard-of-care gemcitabine plus cisplatin. The OS was the primary endpoint of the study.

Patients receiving the triplet regimen did not show a significantly improved OS compared with patients receiving the standard-of-care (median OS 14.0 months vs 12.7 months; P=0.65, see Figure). Progression-free survival data of the 2 study groups confirmed this result (8.2 months vs 6.4 months; P=0.43). Prof. Shroff added that grade 3 or 4 haematologic toxicities were more common in the GCN arm than in the control arm: anaemia (33% vs 22%); neutropaenia (37% vs 28%); thrombocytopenia (20% vs 15%); leukopenia (25% vs 10%). Discontinuation due to toxicity was 24% versus 19% (P=0.26) with GCN versus the standard-of-care.

Figure: No overall survival benefit for triplet regimen versus doublet regimen [2]



The first randomised phase 3 trial in patients with these rare types of cancer did not deliver evidence that supports the addition of nab-paclitaxel to gemcitabine and cisplatin. The experimental arm showed higher haematologic toxicity with no improved OS. Currently, the standard arm should be gemcitabine/cisplatin plus immunotherapy.

1. Shroff RT, et al. JAMA Oncology. 2019;5(6):824–830.
2. Shroff RT, et al. SWOG 1815: A phase III randomized trial of gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin in newly diagnosed, advanced biliary tract cancers. Late-breaking abstract 490, ASCO GI 2023, 19–21 January, San Francisco, CA, USA.

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Posted on 17 March, 2023