Bevacizumab added to neoadjuvant chemotherapy failed to benefit patients with early and locally advanced breast cancer, according to the first Phase III study in such patients.
Meanwhile, the Food and Drug Administration announced that it is taking steps to rescind bevacizumab's indication in metastatic breast cancer.
The new study, known as GeparQuinto and presented at the CTRC-AACR San Antonio Breast Cancer Symposium, involved 1,889 HER2-negative previously untreated women with early or locally advanced primary breast cancer.
Participants in the study, which received support from Sanofi-Aventis and Roche, were randomized to receive epirubicin (at a dose of 90 mg/m2) and cyclophosphamide (at 600 mg/m2) chemotherapy alone or with bevacizumab. Those who showed a response after four cycles were further randomized to four cycles of docetaxel (100 mg/m2) with or without bevacizumab, followed by surgery.
The rate of pathologic complete response (pCR)—defined as having no invasive or noninvasive residual tumor cells in the breast or axillary nodes at the time of surgery—was 15.0% in the chemotherapy-only arm and 17.5% in the bevacizumab arm, a difference that was not statistically significant, reported Gunter von Minckwitz, MD, PhD, Managing Director of the German Breast Group in Neu-Isenburg, Germany.
Gunter von Minckwitz...Image Tools
Breast-Conservation Rates Similar
Even when two less stringent definitions of pathologic complete response—no invasive residual tumor cells in the breast and no invasive residual tumor cells in the breast or nodes—were applied, the pCR rates were still similar between the two groups.
Additionally, the breast-conservation rates were similar in the two arms: 66.6% for chemotherapy alone and 65.8% for bevacizumab.
In subgroup analyses, only women with triple-negative breast tumors not dependent on estrogen or progesterone receptors or HER2 appeared to benefit from bevacizumab, Dr. von Minckwitz said.
The addition of bevacizumab increased the frequency of adverse events, he said.
The rates of serious adverse event rates, primarily febrile neutropenia, nausea, and mucositis, were 23.1% in the group receiving bevacizumab and docetaxel, 15.7% among those who received other chemotherapy and bevacizumab, 12.9% in the group receiving docetaxel with bevacizumab, and 11.8% in the group that had other chemotherapy plus bevacizumab.
Longer Follow-up Needed
Pathologic complete response rates are an accepted surrogate for progression-free survival rates, but their correlation to long-term outcomes and overall survival rates can be determined only with further follow-up, Dr. von Minckwitz said.
“Ongoing studies such as Beatrice [an international Phase III study of adjuvant bevacizumab in triple-negative breast cancer] and long-term survival have to be awaited before drawing definite conclusions.”
Edith A. Perez, MD, Director of the Breast Cancer Program and Professor of Medicine in the Division of Hematology/Oncology at the Mayo Clinic in Jacksonville, FL, said she views neoadjuvant studies such as GeparQuinto as being “essentially hypothesis generating—we have to wait for the data from the adjuvant studies,” she said.
Discussing the study at a Hot Topics session later in the meeting, Hyman B. Muss, MD, Professor of Medicine at the Lineberger Comprehensive Cancer Center at the University of North Carolina, called the results “a little bit disappointing”—“I was surprised to see it was negative,” he said.
© 2011 Lippincott Williams & Wilkins, Inc.