Studies Evaluate Maintenance Bevacizumab in Metastatic Breast Cancer

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Gunter von Minckwitz, MD, PhD

Continuous VEGF suppression appears to be important, consistent with findings in metastatic colorectal cancer.

—Gunter von Minckwitz, MD, PhD

Although bevacizumab (Avastin) may no longer be an active player in metastatic breast cancer, phase III studies presented at this year’s European Society for Medical Oncology (ESMO) Congress reignited interest in the drug as part of maintenance therapy.

The TANIA trial met its primary endpoint, improving progression-free survival when bevacizumab was continued after progression on first-line bevacizumab-containing regimens.1 In the IMELDA trial, the addition of capecitabine to maintenance bevacizumab provided a statistically significant improvement in progression-free survival and overall survival.2


Gunter von Minckwitz, MD, PhD, Chairman of the German Breast Group, Neu-Isenburg, and Professor of Gynecology at the University Women’s Hospital in Frankfurt, Germany, presented the mature prespecified second-line progression-free survival analysis of the TANIA trial, which evaluated the importance of continued suppression of the vascular endothelial growth factor (VEGF) with maintenance therapy.1

TANIA, which was conducted in 12 countries, randomly assigned 494 HER2-negative patients to second-line treatment with a single chemotherapy agent, alone or with bevacizumab, as maintenance. Capecitabine was the investigator’s choice in 60% of patients, and vinorelbine was used by 11%.

“The primary objective was met, showing statistically significant improved progression-free survival with bevacizumab after progressive disease on first-line bevacizumab-containing therapy,” Dr. von Minckwitz reported. “TANIA showed that in bevacizumab-pretreated locally recurrent or metastatic breast cancer, further bevacizumab improves second-line progression-free survival.”

After a median follow-up of approximately 16 months, the median second-line progression-free survival was 6.3 months with chemotherapy plus bevacizumab vs 4.2 months with chemotherapy alone (hazard ratio [HR] = 0.75; P = .0068). All subgroups appeared to benefit from the combination. He noted that the progression-free survival in the control arm was shorter than expected but consistent with subgroup data from contemporary trials evaluating second-line capecitabine.

Stable disease rates increased with the combination (48.9% vs 33.5%), though overall response rates were not substantially better (20.9% vs 16.8%; P = .3457). Second-line safety results were as expected from previous bevacizumab trials.

“Continuous VEGF suppression appears to be important, consistent with findings in metastatic colorectal cancer,” Dr. von Minckwitz suggested.

Biomarker and additional subgroup analyses will be reported at the San Antonio Breast Cancer Symposium in December. Final analysis of overall survival and third-line endpoints is anticipated in 2015.


The open-label randomized phase III IMELDA trial tested whether, after three to six cycles of bevacizumab/docetaxel, maintenance therapy with bevacizumab alone or bevacizumab plus capecitabine would prolong the time until disease progression. Joseph Gligorov, MD, PhD, a medical oncologist at Tenon University Hospital in Paris, presented the findings.2

The study enrolled 287 patients with HER2-negative metastatic disease who had received no prior chemotherapy. After bevacizumab/docetaxel, patients without progressive disease were randomly assigned to continue bevacizumab alone or in combination with capecitabine until disease progression. A total of 185 patients were ultimately assigned to maintenance. The primary endpoint was progression-free survival.

Adding capecitabine to maintenance bevacizumab significantly improved progression-free survival, from 4.3 months with bevacizumab alone to 11.9 months with bevacizumab/capecitabine (HR = 0.38, P < .001). Median overall survival from the time of randomization was also significantly improved, from 23.7 months to 39 months (HR = 0.43, P = .0003), despite the smaller-than-planned sample size (accrual was terminated early). The investigators cautioned that overall survival remains immature, as only 47% of patients have died.

Adverse events were increased in the combination arm, particularly hand-foot syndrome, which occurred in one-third of the patients on the combination and resulted in treatment discontinuation in 10%. Thromboembolism, myocardial infarction, and hypertension were also more common with the doublet.

Dr. Gligorov concluded that in patients benefiting from first-line bevacizumab-containing therapy, continuing bevacizumab with capecitabine improves outcomes. The investigators are now evaluating postprogression regimens and patient-reported outcomes. ■

Disclosure: Drs. von Minckwitz and Gligorov are paid members on Roche’s advisory boards and have received speaker honoraria and conducted Roche-sponsored research.


1. von Minckwitz G, Puglisi F, Cortes J, et al: Efficacy and safety in TANIA, a randomized phase III trial of continued or reintroduced bevacizumab after 1st-line bevacizumab for HER2-negative locally recurrent/metastatic breast cancer. ESMO 2014 Congress. Abstract 353O. Presented September 28, 2014.

2. Gligorov J, Doval D, Bines J, et al: Efficacy and safety of maintenance bevacizumab with or without capecitabine after initial first-line bevacizumab plus docetaxel for HER2-negative metastatic breast cancer: IMELDA randomized phase III trial. ESMO 2014 Congress. Abstract 352O. Presented September 28, 2014.

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