Hope S. Rugo, MD, Professor of Medicine and Director of Breast Oncology and Clinical Trials Education for the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, discussed the two studies on maintenance bevacizumab (Avastin) for metastatic breast cancer presented at the European Society for Medical Oncology (ESMO) Congress in Madrid.

Dr. Rugo summed up TANIA and IMELDA as showing that for patients who respond to first-line treatment, continued maintenance improves outcomes, though the contribution of bevacizumab remains unclear and this drug should not be used as a single agent.

“Extending bevacizumab after progression into the second line prolongs progression-free survival,” she said. The studies suggested the benefit is greatest for patients with estrogen receptor–positive disease and triple-negative tumors. Toxicity was as expected, although these patients had already been shown to tolerate bevacizumab in the first-line setting, she pointed out.

Key Findings

The results of these studies are comparable to those from RIBBON-2, which found median progression-free survival to be 7.2 months for bevacizumab/chemotherapy in the second line (HR = 0.78, P = .0072),¹ Dr. Rugo indicated.

The findings are in accordance with the preclinical rationale for continuing bevacizumab, which counteracts the rapid mobilization of circulating endothelial progenitor cells triggered by chemotherapy. The discontinuation of bevacizumab in previous trials could be one reason they failed to show an overall survival improvement, she suggested.

The TANIA trial asked whether bevacizumab should continue after progression on first-line bevacizumab, and it found a significant improvement in progression-free survival with this approach. The IMELDA study questioned whether instead of maintenance chemotherapy, bevacizumab could be given alone but found that bevacizumab plus chemotherapy was significantly more beneficial.

Dr. Rugo commented that the median progression-free survival for capecitabine/bevacizumab in IMELDA, 11.9 months, is “rarely seen in HER2-negative advanced breast cancer.” Median progression-free survival from the start of first-line treatment, an exploratory endpoint, also doubled to more than 16 months, which is longer than the median progression-free survival of about 11 months observed in three previous randomized phase III trials of bevacizumab plus paclitaxel, she pointed out.

She further commented on the impressive median overall survival of 39 months in IMELDA, with the caveat that fewer than half the patients had died—“a rather pleasant complication to the data analysis in this study of advanced breast cancer.”

Practical Implications

Based on the data from these two studies, Dr. Rugo asked, “Should we continue this expensive drug with known toxicities into the second-line setting in countries where bevacizumab is still approved?” The data on TANIA, on overall survival and biomarker analyses, to be presented at the San Antonio Breast Cancer Symposium, will help answer this question, she said.

“We need to understand how to apply bevacizumab in the clinic in a way that will maintain quality of life, not increase costs, and give an overall survival advantage, where possible,” Dr. Rugo suggested.

She concluded that while maintenance chemotherapy does improve outcomes, “it is unclear what additional benefit we get from bevacizumab, and we need to balance this against cost and toxicity … and bevacizumab alone should not be used for maintenance.”

She concluded, “Bevacizumab clearly has an impact in breast cancer. We just don’t know in whom, and how to use it.” ■

Disclosure: Dr. Rugo has received research funding from Genentech/Roche.

Reference

1. Brufsky AM, Hurvitz S, Perez E, et al: RIBBON-2: A randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2–negative metastatic breast cancer. J Clin Oncol 29:4286-4293, 2011.