Patients with estrogen receptor–positive, HER2-negative advanced or metastatic breast cancer may receive alternative treatment with switch maintenance endocrine therapy and bevacizumab and experience notable efficacy and improved safety vs continued weekly paclitaxel and bevacizumab.
Treatment with switch maintenance endocrine therapy and bevacizumab (Avastin) following bevacizumab/paclitaxel induction is a promising alternative to continued weekly paclitaxel and bevacizumab with a better safety profile in patients with estrogen receptor (ER)–positive, HER2-negative advanced or metastatic breast cancer, according to findings from the phase 2 BOOSTER study (NCT01989780).
After a median follow-up of 21.3 months (interquartile range [IQR], 13.0-28.2), patients in the endocrine therapy group had a significantly longer time to failure of strategy (TFS) at 16.8 months (95% CI, 12.9-19.0) compared with 8.9 months (95% CI, 5.7-13.8) in the weekly paclitaxel plus bevacizumab group (HR, 0.51; 95% CI, 0.34-0.75; P = .0006).
“Treatment of advanced or metastatic breast cancer includes continuation of chemotherapy until disease progression or unacceptable adverse events. To our knowledge, this is the first study showing the benefit of switch maintenance endocrine therapy (endocrine therapy plus bevacizumab) after 4 to 6 cycles of induction chemotherapy (weekly paclitaxel plus bevacizumab). Among responders to induction therapy, the TFS was significantly longer in the endocrine therapy plus bevacizumab maintenance group than in the weekly paclitaxel plus bevacizumab continuation group in patients with ER-positive, HER2-negative advanced or metastatic breast cancer who had not previously been treated with first-line chemotherapy,” the investigators wrote.
To be eligible for the study, patients needed to be between the ages of 20 and 75 years old with histologically confirmed disease. Moreover, patients needed to have advanced disease demonstrating distant metastases or recurrence that was ineligible for surgery, an ECOG performance status of 0 or 1, an estimated life expectancy of at least 3 months, and no prior chemotherapy for advanced or recurrent breast cancer.
Patients received induction chemotherapy that included 4 to 6 cycles of weekly intravenous paclitaxel at 90 mg/m2 on days 1, 8, and 15 and 10 mg/kg of bevacizumab on days 1 and 15 of each cycle. After experiencing a complete response (CR), partial response (PR), or stable disease, patients were randomized 1:1 to either continue treatment with paclitaxel and bevacizumab or switch endocrine therapy and bevacizumab. Patients could receive reinduction with bevacizumab plus paclitaxel is they progressed during endocrine therapy. Treatment only stopped upon disease progression or start of second-line treatment.
The study’s primary end point was TFS, with secondary end points including overall survival (OS), progression-free survival, and safety.
A total of 160 patients enrolled on the study and began induction therapy. Among these patients, 35 were excluded due to disease progression (n = 11), adverse effects (AEs; n = 11), death (n = 2), consent withdrawal (n = 6), or other reasons (n = 5). A total of 125 patients had a CR, PR, or stable disease were randomized to either the endocrine therapy arm (n = 62) or weekly paclitaxel arm (n = 63).
The median ages in the endocrine therapy and paclitaxel arms were 59.0 years (IQR, 47.0-64.0) and 56.0 years (IQR, 49.0-65.0), respectively. Approximately 50% of patients (54% vs 49%, respectively) had liver metastases and most were postmenopausal (70% vs 63%) with an ECOG performance status of 0 (92% vs 81%).
Additional findings from the study indicated that after a median follow-up of 29.3 months, 31 and 33 deaths took place in the weekly paclitaxel and endocrine therapy groups, respectively. OS was similar between groups, with a 2-year rates of 66.9% (95% CI, 53.5%-77.2%) in the endocrine therapy group vs 62.3% (95% CI, 48.5%-77.3%) in the weekly paclitaxel group.
Grade 3 or higher AEs occurred in 38% of those in the endocrine therapy group and 48% of those in the weekly paclitaxel group. The most common grade 3/4 AEs in both respective groups were proteinuria (16% vs 13%), hypertension (10% vs 10%), decreased neutrophil count (8% vs 13%), and peripheral neuropath (2% vs 10%).
Saji S, Taira N, Kitada M, et al. Switch maintenance endocrine therapy plus bevacizumab after bevacizumab plus paclitaxel in advanced or metastatic oestrogen receptor-positive, HER2-negative breast cancer (BOOSTER): a randomised, open-label, phase 2 trial. Lancet Oncol. 2022;23(5):636-649. doi:10.1016/S1470-2045(22)00196-6