Second-Line Bevacizumab/Chemotherapy Improves Progression-Free Survival in Advanced HER2-Negative Breast Cancer
In the phase III TANIA trial reported in The Lancet Oncology, von Minckwitz et al found that adding bevacizumab (Avastin) to chemotherapy in second-line treatment improved progression-free survival after first-line bevacizumab plus chemotherapy in patients with HER2-negative locally recurrent or metastatic breast cancer.
Study Details
This ongoing open-label trial enrolled 494 patients with disease progression after ≥ 12 weeks of first-line bevacizumab plus chemotherapy from 118 centers in France, Hungary, Spain, Italy, Austria, Croatia, Germany, Switzerland, Slovakia, Greece, Israel, and Argentina. Patients were randomly assigned between February 2011 and April 2013 to receive second-line single-agent chemotherapy with (n = 247) or without (n = 247) bevacizumab at 15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks until disease progression, unacceptable toxicity, or consent withdrawal. At progression, patients randomly assigned to chemotherapy alone received third-line chemotherapy without bevacizumab, and those randomly assigned to bevacizumab continued bevacizumab with third-line chemotherapy.
Randomization was stratified by hormone receptor status, first-line progression-free survival from time of diagnosis of locally recurrent or metastatic breast cancer, selected second-line chemotherapy, and lactate dehydrogenase concentration. The primary endpoint was progression-free survival from randomization to second-line progression or death in the intent-to-treat population.
In the bevacizumab/chemotherapy vs chemotherapy group, first-line chemotherapy given along with bevacizumab consisted of paclitaxel in 74% vs 73%, docetaxel in 13% vs 11%, and capecitabine in 16% vs 19%. Second-line chemotherapy included capecitabine in 60% vs 60%, an anthracycline in 15% vs 14%, a taxane in 10% vs 11%, vinorelbine in 12% vs 11%, and gemcitabine in 2% vs 4%.
Improved Progression-Free Survival
Median duration of follow-up for the current analysis was 16.1 months in the combination group and 15.9 months in the chemotherapy-alone group. Median progression-free survival was 6.3 months (95% confidence interval [CI] = 5.4–7.2 months) vs 4.2 months (95% CI = 3.9–4.7 months; stratified hazard ratio [HR] = 0.75, P = .0068). Hazard ratios favored the combination across stratification subgroups. Among patients with measurable disease, objective response was observed in 21% vs 17%.
Adverse Events
Adverse events of grade ≥ 3 occurred in 59% of the combination group vs 46% of the chemotherapy group, with the most common being hypertension (13% vs 7%), neutropenia (12% vs 8%), and hand-foot syndrome (11% vs 11%). Grade 3 proteinuria occurred in 7% vs < 1%. Serious adverse events were reported in 25% vs 18%.
Adverse events led to discontinuation of second-line bevacizumab in 18% of combination patients, most commonly due to proteinuria (5%), venous embolism (2%), and pulmonary embolism (2%), and to discontinuation of chemotherapy in 16% of the combination group and 8% of the chemotherapy group; the most common adverse event leading to discontinuation of chemotherapy was hand-foot syndrome (2% in combination group). Chemotherapy dose reductions were required in 47% vs 37% of patients.
The investigators concluded: “These results suggest that continued VEGF inhibition with further bevacizumab is a valid treatment option for patients with locally recurrent or metastatic HER2-negative breast cancer whose disease was stabilised or responded to first-line bevacizumab with chemotherapy.”
Gunter von Minckwitz, MD, of the German Breast Group, Neu-Isenburg, and University Women’s Hospital, Frankfurt, is the corresponding author for The Lancet Oncology article.
The study was funded by F. Hoffmann-La Roche. For full disclosures of the study authors, visit www.thelancet.com.
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