Taxane-Based Chemotherapy in Triple-Negative Breast Cancers
Taxane-Based Chemotherapy in Triple-Negative Breast Cancers
Background: We evaluated the pathological complete response (pCR) rate after neoadjuvant epirubicin, (E) cyclophosphamide (C) and docetaxel containing chemotherapy with and without the addition of bevacizumab in patients with triple-negative breast cancer (TNBC).
Patients and methods: Patients with untreated cT1c-4d TNBC represented a stratified subset of the 1948 participants of the HER2-negative part of the GeparQuinto trial. Patients were randomized to receive four cycles EC (90/600 mg/m; q3w) followed by four cycles docetaxel (100 mg/m; q3w) each with or without bevacizumab (15 mg/kg; q3w) added to chemotherapy.
Results: TNBC patients were randomized to chemotherapy without (n = 340) or with bevacizumab (n = 323). pCR (ypT0 ypN0, primary end point) rates were 27.9% without and 39.3% with bevacizumab (P = 0.003). According to other pCR definitions, the addition of bevacizumab increased the pCR rate from 30.9% to 41.8% (ypT0 ypN0/+; P = 0.004), 36.2% to 46.4% (ypT0/is ypN0/+; P = 0.009) and 32.9% to 43.3% (ypT0/is ypN0; P = 0.007). Bevacizumab treatment [OR 1.73, 95% confidence interval (CI) 1.23–2.42; P = 0.002], lower tumor stage (OR 2.38, 95% CI 1.24–4.54; P = 0.009) and grade 3 tumors (OR 1.68, 95% CI 1.14–2.48; P = 0.009) were confirmed as independent predictors of higher pCR in multivariate logistic regression analysis.
Conclusions: The addition of bevacizumab to chemotherapy in TNBC significantly increases pCR rates.
Patients with triple-negative breast cancer (TNBC) are at highest risk of relapse and death among all breast cancer subtypes. At present, anthracycline–taxane-based chemotherapy represents the standard of care for TNBC patients, as no specific treatments are available for this heterogeneous disease. TNBC is highly proliferative, with an enhanced angiogenesis, high intratumoral vascular endothelial growth factor (VEGF) levels and activation of genes involved in angiogenesis. Therefore, anti-angiogenic drugs may be particularly effective. Bevacizumab, a monoclonal antibody directed against the VEGF-A ligand, has shown clinical efficacy in patients with metastatic TNBC.
In the GeparQuinto study, we have shown that addition of bevacizumab to neoadjuvant chemotherapy significantly increased the pCR rate in HER2-negative early-stage breast cancer. The most notable and pronounced pCR rate was seen in the TNBC subgroup. Moreover, TNBC is the subtype with the greatest difference in disease-free and overall survival in patients with and without pCR after neoadjuvant chemotherapy.
The GeparQuinto trial was designed to compare the pCR rates in patients with HER2-negative primary breast cancer. A secondary objective was to analyze the effect of bevacizumab in the predefined and stratified subgroup of TNBC patients.
Abstract and Introduction
Abstract
Background: We evaluated the pathological complete response (pCR) rate after neoadjuvant epirubicin, (E) cyclophosphamide (C) and docetaxel containing chemotherapy with and without the addition of bevacizumab in patients with triple-negative breast cancer (TNBC).
Patients and methods: Patients with untreated cT1c-4d TNBC represented a stratified subset of the 1948 participants of the HER2-negative part of the GeparQuinto trial. Patients were randomized to receive four cycles EC (90/600 mg/m; q3w) followed by four cycles docetaxel (100 mg/m; q3w) each with or without bevacizumab (15 mg/kg; q3w) added to chemotherapy.
Results: TNBC patients were randomized to chemotherapy without (n = 340) or with bevacizumab (n = 323). pCR (ypT0 ypN0, primary end point) rates were 27.9% without and 39.3% with bevacizumab (P = 0.003). According to other pCR definitions, the addition of bevacizumab increased the pCR rate from 30.9% to 41.8% (ypT0 ypN0/+; P = 0.004), 36.2% to 46.4% (ypT0/is ypN0/+; P = 0.009) and 32.9% to 43.3% (ypT0/is ypN0; P = 0.007). Bevacizumab treatment [OR 1.73, 95% confidence interval (CI) 1.23–2.42; P = 0.002], lower tumor stage (OR 2.38, 95% CI 1.24–4.54; P = 0.009) and grade 3 tumors (OR 1.68, 95% CI 1.14–2.48; P = 0.009) were confirmed as independent predictors of higher pCR in multivariate logistic regression analysis.
Conclusions: The addition of bevacizumab to chemotherapy in TNBC significantly increases pCR rates.
Introduction
Patients with triple-negative breast cancer (TNBC) are at highest risk of relapse and death among all breast cancer subtypes. At present, anthracycline–taxane-based chemotherapy represents the standard of care for TNBC patients, as no specific treatments are available for this heterogeneous disease. TNBC is highly proliferative, with an enhanced angiogenesis, high intratumoral vascular endothelial growth factor (VEGF) levels and activation of genes involved in angiogenesis. Therefore, anti-angiogenic drugs may be particularly effective. Bevacizumab, a monoclonal antibody directed against the VEGF-A ligand, has shown clinical efficacy in patients with metastatic TNBC.
In the GeparQuinto study, we have shown that addition of bevacizumab to neoadjuvant chemotherapy significantly increased the pCR rate in HER2-negative early-stage breast cancer. The most notable and pronounced pCR rate was seen in the TNBC subgroup. Moreover, TNBC is the subtype with the greatest difference in disease-free and overall survival in patients with and without pCR after neoadjuvant chemotherapy.
The GeparQuinto trial was designed to compare the pCR rates in patients with HER2-negative primary breast cancer. A secondary objective was to analyze the effect of bevacizumab in the predefined and stratified subgroup of TNBC patients.
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