Updated results confirm that addition of bevacizumab to docetaxel as first-line breast cancer treatment improves survival and response rates.
San Antonio, TX — Updated results of the AVADO trial confirm previously reported interim findings: the addition of bevacizumab (Avastin) to docetaxel (Taxotere) as first-line treatment of locally recurrent or metastatic breast cancer improves progression-free survival (PFS) and objective response rates (ORR). The addition of bevacizumab did not appear to affect the safety profile of docetaxel treatment.
Although overall survival (OS) was not significantly different between patients who received a lower dose of bevacizumab and those who took a higher dose, David Miles, MD, said that OS may have been influenced by crossover in this trial and the affect of subsequent therapies. Dr Miles is consultant medical oncologist at Mount Vernon Hospital in Northwood, Middlesex, U.K.
AVADO is the most recent of three trials that show adding bevacizumab to chemotherapy in the first-line setting improves PFS and ORR in metastatic breast cancer. The results Dr Miles presented at the San Antonio Breast Cancer Symposium were the final OS data, along with updated data on other endpoints, including time to progression (TTP) and duration of response. He did not have time to present quality of life data, but at a press conference, he said patients on bevacizumab had improved quality of life in this trial.
Within 1 year, AVADO had recruited 736 patients from 104 sites across 26 countries. Median age was 55 years; two-thirds of the patients received adjuvant chemotherapy (25% were treated with taxanes); more than 80% had measurable disease at study entry.
Patients were randomized to one of three arms: docetaxel plus placebo; docetaxel plus 7.5 mg/kg of bevacizumab every 3 weeks or docetaxel plus 15 mg/kg of bevacizumab every 3 weeks. Patients could receive a maximum of 9 cycles but could stop after 6 cycles. If chemotherapy was discontinued, placebo and bevacizumab were continued until disease progression. Crossover was allowed after unblinding of study results, Dr Miles said.
At a median follow-up of 25 months, updated data showed median PFS was 9 months for the lower-dose bevacizumab group versus 8.2 months for docetaxel alone, representing a 14% risk reduction in disease progression or death. Median PFS was significantly improved with the higher dose of bevacizumab compared with placebo, at >10 months compared with 8.2 months (P = .006), representing a 23% risk reduction.
A separate analysis censored for non-protocol therapy before disease progression (encompassing only 3% of patients) found that median PFS was 10 months for the 15-mg dose of bevacizumab group versus >8 months for the placebo arm, representing a 33% risk reduction (P=.002). A similar censored analysis for the 7.5-mg arm of the trial showed a median PFS of 8.1 months for the placebo arm and 9 months for the bevacizumab arm.
The ORR was 64.1% for the higher dose of bevacizumab, 55% for the lower dose, and 46% for placebo. The difference in ORR between bevacizumab and placebo was considered highly significant (P = .0003).
The rate of 1-year survival was 84% in the group receiving the higher dose of bevacizumab compared with 76% for the placebo group (P = .0003).No significant differences were seen in OS between the two bevacizumab groups.
Neutropenia was an expected complication, Dr Miles said. Grade 3 or higher neutropenia was reported in 17.3% of the control arm and 19.8% in each of the two bevacizumab-containing arms. Grade 3 or higher hypertension was seen in 1.3% of the placebo group compared with 0.8%, and 4.8% in the bevacizumab arms. Hypertension requiring treatment was reported in 11% of patients in the lower-dose bevacizumab arm and 18% of patients in the higher-dose arm. No increase in GI perforation, wound healing, bleeding, or thrombotic events was reported with bevacizumab treatment. “This is reassuring,” Dr Miles said. SABCS Abstract 41.
Disclosure: The study was supported by Hoffman-LaRoche.