Endocrine therapy plus bevacizumab with the possibility of weekly paclitaxel reinduction signals efficacy and demonstrates a good safety profile in patients with ER-positive, HER2-negative advanced or metastatic breast cancer who have responded to induction therapy.
Switch maintenance to endocrine therapy plus bevacizumab (Avastin) with the possibility of weekly paclitaxel reinduction signals efficacy and demonstrates a better safety profile compared to weekly paclitaxel plus bevacizumab in patients with estrogen receptor (ER)-positive, human epidermal receptor (HER)2-negative advanced or metastatic breast cancer who have responded to induction therapy, according phase 2 study findings published in the Lancet Oncology.1
BOOSTER is a multicenter, randomized study ( NCT01989780), which compared continuing bevacizumab and paclitaxel or switching to hormonal maintenance therapy followed by bevacizumab plus paclitaxel after induction therapy of bevacizumab plus paclitaxel, in order to evaluate optimal usage.
The study enrolled a total of 160 patients with advanced or metastatic ER-positive, HER2-negative breast cancer across 53 hospitals in Japan with the goal of comparing the 2 treatment strategies following induction therapy with 4-6 cycles of the combined use of weekly paclitaxel and bevacizumab.2
Enrollment in the trial was open to females aged 20-75 with histologically confirmed adenocarcinoma of the breast who had HER2-negative disease and documented ER-positive. At the time of enrollment, the locally advanced or metastatic breast cancer had to be inoperative, and patients must have had no prior systemic therapy. Other requirements included an ECOG performance status of 0 or 1, a life expectancy at a minimum of 3 months, a measurable lesion per RECIST criteria, and adequate following organ function within 2 weeks before starting treatment.
Every patient received 4 to 6 cycles of weekly, intravenous (IV) paclitaxel at 90 mg/m2 on days 1, 8, and 15 of each cycle and bevacizumab induction therapy in addition to IV bevacizumab at 10 mg/kg on days 1 and 15 of each. Responders who showed a complete response, partial response, or stable disease after induction therapy were then randomly assigned in a 1:1 ratio to either continue weekly paclitaxel plus bevacizumab or switch to maintenance endocrine therapy plus bevacizumab.
A total of 125 (78%) patients were then randomly assigned to endocrine therapy plus bevacizumab (n = 62; n = 61 in the full analysis set) or to weekly paclitaxel plus bevacizumab (n = 63; n = 63 in the full analysis set). In arm A, paclitaxel and bevacizumab was continued, while in arm B, paclitaxel was switched to maintenance endocrine therapy until disease progression, followed by paclitaxel and bevacizumab re-induction.
The primary end point was time to failure of strategy (TFS), which is 3.5 years or the time from randomization to a qualifying event. Secondary end points included overall survival, 2-year overall survival rate, progression-free survival, quality of life, and safety.
At a median follow-up of 21.3 months (13.0–28.2), TFS was significantly longer within the group of patients to receive endocrine therapy plus bevacizumab group (median 16.8 months, 95% CI, 12.9-19.0) vs in the weekly paclitaxel plus bevacizumab group (8.9 months, 5.7-13.8; HR, 0.51, 0.34-0.75; P =0.0006).
In regard to safety, the most common grade 3 or 4 non-hematological adverse events (AEs) reported in the endocrine therapy plus bevacizumab group after randomization were 16% proteinuria (n = 10), 10% hypertension (n = 6), and 2% peripheral neuropathy (n = 1). In the weekly paclitaxel plus bevacizumab group, grade 3 or 4 non-hematological AEs that occurred included 13% proteinuria (n = 8), 10% hypertension (n = 6), and 10% peripheral neuropathy (n = 6). Further, 1 treatment-related death was reported in the weekly paclitaxel plus bevacizumab group due to duodenal ulcer perforation.
Overall, the study showed switching to maintenance endocrine therapy in addition to bevacizumab to be an efficacious alternative, when given the possibility of weekly paclitaxel reinduction, compared to continuing weekly paclitaxel plus bevacizumab in this patient population.