In the Japanese phase II BOOSTER trial reported in The Lancet Oncology, Saji et al found that compared with continuing paclitaxel/bevacizumab, a maintenance strategy of switching to endocrine therapy plus bevacizumab (with the option of reinitiating paclitaxel/bevacizumab) was associated with a longer time to treatment failure among women with estrogen receptor–positive, HER2-negative advanced breast cancer with at least stable disease on first-line induction with paclitaxel/bevacizumab.

Study Details

In the multicenter open-label trial, 160 patients enrolled between January 2014 and December  2015 were treated with an induction regimen of four to six 28-day cycles of weekly paclitaxel at 90 mg/m² on days 1, 8, and 15 plus bevacizumab at 10 mg/kg on days 1 and 15. Patients with a complete or partial response or stable disease were randomly assigned to continue weekly paclitaxel/bevacizumab or switch to maintenance endocrine therapy (aromatase inhibitor or fulvestrant with or without ovarian function suppression) plus bevacizumab. Patients could receive weekly paclitaxel/bevacizumab reinduction if they had disease progression with maintenance endocrine therapy plus bevacizumab.

The primary endpoint was time to failure of strategy, defined as the time from randomization to death, disease progression during or after the end of the planned treatment, start of drug therapy other than the stipulated treatment, or disease progression after the first stipulated treatment but no initiation of the subsequent stipulated treatment within 1 month (applicable only to the endocrine therapy/bevacizumab group).

Time to Failure of Strategy

Of a total of 125 patients (78%) with at least stable disease on induction, 124 evaluable patients  were randomly assigned to receive endocrine therapy plus bevacizumab (n = 61) or to continue weekly paclitaxel plus bevacizumab (n = 63). Among the 61 patients in the endocrine therapy/bevacizumab group, 32 (52%) were reinitiated on weekly paclitaxel/bevacizumab after clinical disease progression.

At a median follow-up of 21.3 months (interquartile range [IQR] = 13.0–28.2 months), median time to failure of strategy was 16.8 months (95% confidence interval [CI] = 12.9–19.0 months) in the endocrine therapy/bevacizumab group vs 8.9 months (95% CI = 5.7–13.8 months) in the paclitaxel/bevacizumab group (hazard ratio [HR] = 0.51, 95% CI = 0.34–0.75, P = .0006).

In the paclitaxel/bevacizumab group, the median duration of treatment was 5.8 months. Among the 32 patients in the endocrine therapy/bevacizumab group who received reinduction with paclitaxel/bevacizumab, the median time from reinduction therapy to a time to failure of strategy event was 7.0 months and the median duration of reinduction treatment was 6.0 months.

After a median follow-up of 29.3 months (IQR = 16.3–40.3 months), median overall survival was 37.4 months (95% CI = 27.3 months to not reached) in the endocrine therapy/bevacizumab group vs 39.0 months (95% CI = 22.9 months to not reached) in the paclitaxel/bevacizumab group (HR = 0.98, 95% CI = 0.60–1.61, P = .94); 2-year overall survival rates were 66.9% vs 62.3%.

Adverse Events

Grade ≥ 3 adverse events occurred in 38% of the endocrine therapy/bevacizumab group vs 48% of the paclitaxel/bevacizumab group. The most common in both groups were proteinuria (16% vs 13%), hypertension (10% vs 10%), decreased neutrophil count (8% vs 13%), and peripheral neuropathy (2% vs 10%).  One treatment-related death, due to duodenal ulcer perforation, occurred in a patient in the paclitaxel/bevacizumab group.

The investigators concluded: “Switch to maintenance endocrine therapy plus bevacizumab with the possibility of weekly paclitaxel reinduction if needed is an efficacious alternative, with a better safety profile, to continuing weekly paclitaxel plus bevacizumab in patients with [estrogen receptor–]positive, HER2-negative advanced or metastatic breast cancer who have responded to induction therapy.”

Shigehira Saji, MD, of the Department of Medical Oncology, Fukushima Medical University Hospital, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Chugai Pharmaceutical. For full disclosures of the study authors, visit thelancet.com.