Biliary Tract Cancer · Medical · Advanced/Metastatic · First-line

In advanced biliary tract cancer, does cisplatin plus gemcitabine improve survival compared with gemcitabine alone? [ABC-02]

In advanced biliary tract cancer, does cisplatin plus gemcitabine improve survival compared with gemcitabine alone?

Population

410 patients with locally advanced or metastatic biliary tract cancer, including cholangiocarcinoma and gallbladder cancer, with adequate organ function.

Sample size

410 randomized patients.

Intervention vs comparator

Cisplatin 25 mg/m² plus gemcitabine 1,000 mg/m² on days 1 and 8 every 21 days for up to six cycles versus gemcitabine alone 1,000 mg/m² on days 1, 8 and 15 every 28 days.

Primary endpoint

Primary endpoint: overall survival; PFS and disease control were key secondary outcomes.

Absolute Effect

Median OS was 11.7 months with cisplatin/gemcitabine versus 8.1 months with gemcitabine alone; HR approximately 0.64, P<.001.

Absolute effect: The median survival difference was 3.6 months. PFS was 8.0 vs 5.0 months. Because medians are not fixed-time event rates, an NNT for OS is not calculated.

NNT: not quantifiable from median OS alone; no defensible fixed-time OS event-rate difference is used.

NNH: 13, based on grade 3–4 neutropenia (25.3% vs approximately 17%; absolute increase about 8 percentage points).

Follow-up: The phase III publication followed the preceding randomized phase II experience and established the regimen as the reference chemotherapy backbone.

Clinical results and treatment burden

Intervention: Cisplatin 25 mg/m² plus gemcitabine 1,000 mg/m² on days 1 and 8 every 21 days for up to six cycles versus gemcitabine alone 1,000 mg/m² on days 1, 8 and 15 every 28 days.
Principal toxicity: Overall grade 3–4 adverse-event frequency was similar (70.7% vs 68.8%), but neutropenia was more frequent with cisplatin/gemcitabine. Treatment discontinuation due to toxicity was similar (10.4% vs 8.6%).
Other efficacy/recurrence findings: Quality-of-life measures did not show a clinically important overall deterioration with combination treatment.
Quality of life: Longitudinal EORTC QLQ-C30 analyses did not show broad QoL harm from cisplatin/gemcitabine; digestive symptoms and appetite loss favoured the combination in adjusted analyses.

Eligibility and clinical context

410 patients with locally advanced or metastatic biliary tract cancer, including cholangiocarcinoma and gallbladder cancer, with adequate organ function.

Limitations and maturity: The trial predates modern molecular classification and immunotherapy combinations. Results establish the chemotherapy backbone but do not answer current questions about immunotherapy selection or molecularly defined subgroups.

Clinical interpretation

ABC-02 established cisplatin plus gemcitabine as a high-value systemic foundation for advanced biliary tract cancer, with a clear survival gain without a major increase in overall severe toxicity.

Primary / authoritative source

Valle J, et al. N Engl J Med. 2010;362:1273–1281.