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Ramucirumab offered no benefit in metastatic HER-2–negative breast cancer
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The addition of ramucirumab to first-line docetaxel chemotherapy did not significantly improve survival in women with HER-2–negative advanced breast cancer, according to results of the randomized, phase 3 ROSE/TRIO-012 trial.
Although antiangiogenic strategies have conferred modest PFS improvements in patients with metastatic breast cancer, they have not been shown to improve the quality of survival or OS. Consequently, the evaluation of other agents in a placebo-controlled setting is warranted, according to background information provided by researchers.
John R. Mackey
In the current multinational, double-blind, placebo-controlled study, John R. Mackey, MD, professor of medical oncology at University of Alberta and director of the Clinical Trials Unit at Cross Cancer Institute, and colleagues sought to assess the addition of ramucirumab (Cyramza, Lilly) to docetaxel in women with unresectable, locally recurrent or metastatic HER-2–negative breast cancer.
The analysis included 1,144 women. At baseline, 76% of patients had HER-2–positive breast cancer and 24% had triple-negative disease.
Researchers randomly assigned 385 women to 75 mg/m2 docetaxel plus placebo every 3 weeks. The other 759 women received docetaxel plus 10 mg/kg ramucirumab, a fully human monoclonal antibody that targets vascular endothelial growth factor receptor-2.
PFS served as the primary outcome measure. Secondary outcomes included OS, time to progression, overall response metrics, safety and quality of life.
Median follow-up was 18.6 months.
Results showed women assigned ramucirumab plus docetaxel experienced longer median PFS (9.5 months vs. 8.2 months; HR=0.88; P=.077) and longer median OS (27.3 months vs. 27.2 months; HR=1.01; P=.915), but the differences were not statistically significant.
PFS and OS also were similar between predefined clinical subgroups, including those that evaluated outcomes in patients based on prior taxane therapy, visceral metastasis and hormone receptor status.
Researchers also reported longer median time to progression (9.7 months vs. 8.2 months; HR=0.85; P=.033), a higher objective response rate (44.7% vs. 37.9%; P=0.27) and a higher disease control rate (86.4% vs. 81.3%; P=.022) among women assigned ramucirumab.
Results of a subset analysis that examined patients whose best response was complete or partial response showed median duration of response was longer in the ramucirumab arm (8.4 months vs. 8.1 months; HR=0.84; P=.15).
Fatigue, hypertension, febrile neutropenia, palmer-plantar erythrodysesthesia syndrome and stomatitis were more common in women assigned ramucirumab.
“Protocol-specified correlative assessments are under way to identify molecularly defined populations with ramucirumab-sensitive disease,” Mackey and colleagues wrote. “Ultimately, a better understanding of breast cancer responses to available antiangiogenic therapies and assays to identify relevant biomarkers and sensitive patients are needed for antiangiogenic therapy for breast cancer to fulfill its original promise.”
Disclosure: See the full study for a list of the researchers’ relevant financial disclosures.
Perspective
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Adam M. Brufsky, MD, PhD, FACP
Over the past 5 to 10 years, investigators in metastatic breast cancer have attempted through multiple clinical trials to demonstrate the worth — or lack thereof — of angiogenesis inhibition in the treatment of metastatic breast cancer. In this latest attempt, investigators used ramucirumab, an antibody against the VEGF-2 receptor, in combination with docetaxel to attempt to improve outcomes in the first-line treatment of metastatic breast cancer. Although PFS was marginally improved from 8.2 months to 9.5 months, OS was not changed. This result was disappointing but consistent with other trials of angiogenesis inhibition in metastatic breast cancer. We continue to search for indications of angiogenesis inhibitors in metastatic breast cancer.
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