Disease-free, overall survival unchanged by gemcitabine plus adjuvant chemotherapy

Adding gemcitabine/paclitaxel couplet to epirubicin/cyclophosphamide did not improve disease-free or overall survival in patients with early-stage breast cancer.

Christopher J. Poole, MD, senior lecturer in the cancer research center at the Institute for Cancer Studies in Birmingham, UK, presented the results of the tAnGo trial at the 2008 ASCO Annual Meeting. The multicenter, phase-3 trial included 3,152 patients with early-stage breast cancer.

Patients were randomly assigned to either a control or research arm. The control arm had four cycles of IV epirubicin 90 mg/m² and IV cyclophosphamide 600 mg/m² on day one every three weeks followed by four cycles of paclitaxel 175 mg/m²/three-hour infusion on day one and IV gemcitabine 1,250 mg/m² on days one and eight every three weeks.

About 66% of patients had node positive disease and 41% of patients in each arm had estrogen-receptor negative tumors. A minimum of 30 months follow-up was completed by 60% of patients.

The researchers observed no difference in disease-free (HR=1.0; 95% CI, 0.8 to 1.2) or overall survival (HR=1.1; 95% CI, 0.9 to 1.4) between the two treatment groups.

“The addition of gemcitabine to adjuvant chemotherapy with EC-T at this dose and schedule confers no therapeutic advantage for women with higher risk early stage breast cancer,” Poole said. – by Stacey L. Adams

The combination of gemcitabine and paclitaxel has been shown to be superior to paclitaxel alone in the treatment of metastatic breast cancer, producing superior progression-free and overall survival. Some variant of crossover anthracycline-cyclophosphamide followed by singulation paclitaxel was perhaps the most widely used type of adjuvant chemotherapy regimen in the world at the time of inception of this trial and one which lent itself to the evaluation of the paclitaxel/gemcitabine doublet. The tAnGo investigators compared this doublet to single agent paclitaxel as crossover following epirubicin-cyclophosphamide in the treatment of patients with node-positive disease. The design was well-balanced with eight cycles in each arm, the same doses and a muscular dose of gemcitabine. The study was large and appropriately powered. On the basis of the metastatic data, a demonstration for an adjuvant benefit for the gemcitabine-containing combination would have seemed like a pretty good bet to take in advance of the trial. However, prediction is very difficult, especially when it is about the future, and it can be very difficult sometimes to pick the winner in advance of a race. However, perhaps surprisingly, the study was negative with no demonstratable advantage in disease-free or in overall survival. The most likely explanation for this is that the results are just entirely correct. Namely, gemcitabine in this dosing schedule does not add to the results of thrice weekly anthracycline/cyclophosphamide/paclitaxel in the treatment of patients with early stage breast cancer. It is possible that there is a benefit and that the result is a fluke – though that seems very unlikely.

– John Crown, MD

Professor of Oncology, St. Vincent’s Private Hospital, Dublin, Ireland

For more information:
Poole CJ. tAnGo: A randomized phase-III trial of gemcitabine (gem) in paclitaxel-containing, epirubicin/cyclophosphamide-based, adjuvant chemotherapy (CT) for women with early-stage breast cancer (EBC). #506. Presented at: 2008 ASCO Annual Meeting; May 30-June 2, 2008; Chicago.