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Bevacizumab improves pathological complete response in HER-2–negative early breast cancer
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The addition of four cycles of bevacizumab to standard neoadjuvant chemotherapy significantly improved the pathological complete response rate among patients with HER-2–negative early-stage breast cancer, according to the results of a phase 3 study.
However, the impact of improved pathological complete response on OS and DFS remains undetermined, according to the researchers.
“Survival rates from early-stage breast cancer have improved substantially over the past 20 years,” Helena M. Earl, MBBS, of the department of oncology at the University of Cambridge School of Clinical Medicine, and colleagues wrote. “Although considerable progress has been made in early-stage breast cancer through large adjuvant randomized treatment trials, these advances have been relatively slow.”
The researchers initiated the randomized, open label phase 3 ARTemis trial to evaluate the safety and efficacy of adding bevacizumab (Avastin, Genentech) to a chemotherapy regimen composed of docetaxel, fluorouracil, epirubicin and cyclophosphamide (D-FEC).
The analysis included data from 781 women with newly diagnosed HER-2–negative early-stage invasive breast cancer who received treatment at 66 U.K. National Cancer Research Network centers between 2009 and 2013.
Patients received three cycles of docetaxel (100 mg/m2) once every 21 days, followed by three cycles of fluorouracil (500 mg/m2), epirubicin (100 mg/m2) and cyclophosphamide (500 mg/m2) once every 21 days, with (n = 388) or without (n = 393) four cycles of bevacizumab (15 mg/kg).
Pathological complete response — defined as the absence of invasive disease in the breast and axillary lymph nodes — served as the primary endpoint. Pathological complete response or minimal residual disease in the breast alone — defined as 10% or less of the original tumor burden remaining at time of surgery — served as secondary endpoints.
Twenty percent of all patients (n = 153) achieved a pathological complete response. A significantly higher response rate occurred in the bevacizumab arm, compared with women who received D-FEC alone (22% vs. 17%; P = .03).
Further, patients in the bevacizumab arm achieved significantly higher pathological complete response rates in the breast alone (26% vs. 19%; P = .02) and rates of pathological complete response or minimal residual disease in the breast alone (36% vs. 29%; P = .03).
The researchers observed no patient deaths during chemotherapy or within 4 months of chemotherapy completion. Additionally, no deaths occurred due to cohort assignment.
A total of 461 serious adverse events occurred (bevacizumab plus D-FEC = 265; D-FEC alone = 196). Adverse events occurred at expected levels in both arms; however, incidence of grade 4 neutropenia occurred at a higher rate among patients assigned bevacizumab (22% vs. 17%).
The researchers will begin analyzing the effect of pathological complete response on DFS and OS in 2016. They expect a median follow-up of at least 36 months or 120 DFS events to report outcomes.
The researchers also hope to identify independent biomarkers for bevacizumab response.
“The recent report at the ASCO 2014 annual meeting of an expression signature for angiogenesis in ovarian cancer is an exciting development,” Earl and colleagues concluded. “These results need to be tested prospectively in other datasets. The translational ARTemis trial group plan to explore, using samples from the ARTemis trial biobank, whether the same angiogenic signature in breast cancer could provide a predictive biomarker of response to bevacizumab.” – by Cameron Kelsall
Disclosure: Cancer Research U.K., Roche and Sanofi-Aventis provided funding for the study. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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