Giving BEEP Before WBRT May Improve Control of Brain Metastases in Breast Cancer

Bevacizumab, etoposide, and cisplatin (BEEP) given before whole-brain radiotherapy (WBRT) may help control brain metastases in patients with breast cancer, according to research published in JAMA Oncology.

Patients treated with BEEP before WBRT had improvements in brain-specific progression-free survival (PFS) when compared to patients who received WBRT alone.

These findings come from the phase 2 A-PLUS trial (ClinicalTrials.gov Identifier: NCT02185352), which included 118 breast cancer patients with brain metastases.

All patients were WBRT-naïve at baseline and had at least 1 measurable brain metastatic lesion. The median patient age was 56 (range, 34-71) years, all patients were women, and 62.5% had hormone receptor-positive breast cancer.

Treatment Details

In the intent-to-treat population of 112 patients, 74 were randomly assigned to receive 3 cycles of BEEP followed by WBRT, and 38 patients were assigned to receive WBRT alone.

Patients could receive hormonal therapy, trastuzumab, bisphosphonate, and denosumab during BEEP, but they could not receive other systemic anticancer therapies. Systemic anticancer therapies were also discouraged during WBRT.

Patients could receive systemic treatments after WBRT at the investigators’ discretion, but patients could not receive BEEP or bevacizumab plus cisplatin/carboplatin (BP) without evidence of progression.

After study treatment, 31.1% of patients in the BEEP arm and 31.6% of those in the WBRT-alone arm went on to receive capecitabine plus lapatinib. Another 29.7% of patients in the BEEP arm and 31.6% in the WBRT-alone arm received BEEP or BP after WBRT. After progression, 10.8% of patients in the BEEP arm and 15.8% of those in the WBRT-alone arm received a second round of WBRT.

Results

After completion of study treatment, the response rate was 64.9% in the BEEP arm and 76.3% in the WBRT-alone arm. The disease control rate was 91.9% and 89.5%, respectively.

The median brain-specific PFS was 8.1 months in the BEEP arm and 6.5 months in the WBRT-alone arm (hazard ratio [HR], 0.71; 95% CI, 0.44-1.13; P =.15). This met the predefined threshold for significance (HR, 0.60; 2-sided ɑ ≤.20).

The proportion of patients without brain-specific progression at 8 months was 48.7% in the BEEP arm and 26.3% in the WBRT-alone arm (P =.03).

The median overall survival was 15.9 months in the BEEP arm and 16.4 months in the WBRT-alone arm (HR, 1.08; 95% CI, 0.69-1.68; P =.75).

Serious adverse events (AEs) occurred in 27% of patients in the BEEP arm and 29% of those in the WBRT-alone arm.

The most common AEs in the BEEP arm were neutropenia (30.2%), nausea (27.9%), anemia (27.4%), and leukopenia (24.2%). The most common grade 3-4 AEs in the BEEP arm were neutrophil count decrease (14.9%), white blood cell count decrease (5.1%), and hypertension (3.3%).

“The findings suggest that BEEP addresses an unmet need for an effective systemic treatment for intractable brain and extracranial metastases from metastatic breast cancer,” the researchers concluded.

Disclosures: This research was supported by Roche Taiwan and Chugai Pharma Taiwan. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor