Bevacizumab/Chemo Before WBRT May Better Control Breast Cancer Brain Metastases

The study’s primary end point was brain-specific PFS, with secondary end points including the efficacy of 3 cycles of BEEP vs WBRT, and 2-month brain-specific overall response rate (ORR). Additionally, other prespecified study end points included 8-month brain-specific PFS, extra–central nervous system PFS, PFS, and overall survival.

Treatment with bevacizumab (Avastin), etoposide, and cisplatin (BEEP) prior to whole brain radiotherapy (WBRT) appeared to improve control of brain metastases from breast cancer (BMBC) over WBRT alone, according to results from the phase 2 A-PLUS trial (NCT02185352).

Investigators reported that the median brain-specific progression-free survival (PFS) was 8.1 months (95% CI, 0.3-29.5) among patients who received BEEP compared with 6.5 months (95% CI, 0.9-25.5) in the WBRT alone arm (HR, 0.71; 95% CI, 0.44-1.13; P = .15). Additionally, the 8-month brain-specific PFS rate was 48.7% in the experimental arm vs 26.3% in the experimental arm (P = .03). Data from a masked central review yielded comparable findings of 45.9% vs 26.3%, respectively (P = .03). Moreover, the 2-month brain-specific objective response rate was 41.9% with BEEP compared with 52.6% in the WBRT cohort, the difference of which was not statistically significant.

The open label, multicenter clinical trial included patients between 20 to 75 years old who were diagnosed with invasive breast cancer with 1 or more brain metastases that were 10 mm or larger. Moreover, patients couldn’t have received prior WBRT and must’ve had a Karnofsky performance status (KPS) of 30% or higher. Those with leptomeningeal metastases and/or who were eligible for and assented to surgery or stereotactic radiosurgery as an initial treatment for brain metastases were ineligible for the study.

WBRT was administered at 3000 cGy in 10 fractions over 14 days or less and no more than 1 fraction per day in the comparator cohort while it was given within 28 days of starting the third cycle of BEEP following first brain imaging at 8 weeks in the experimental cohort. For those who were unable to complete 3 cycles of BEEP, WBRT would be administered within 14 days of treatment discontinuation.

Treatment with BEEP consisted of 15 mg/kg of intravenous bevacizumab on day 1; 70 mg/m2 of cisplatin on day 2; and 70 mg/m2 of etoposide on days 2 to 4. Prophylactic granulocyte colony-stimulating factor (GCSF) could be utilized at the investigators’ discretion between 2 to 4 days after every cycle.

The study’s primary end point was brain-specific PFS, with secondary end points including the efficacy of 3 cycles of BEEP vs WBRT, and 2-month brain-specific overall response rate (ORR). Additionally, other prespecified study end points included 8-month brain-specific PFS, extra–central nervous system PFS, PFS, and overall survival.

The study included a total of 118 patients who were randomly assigned to treatment across 8 study sites from September 9, 2014, to December 24, 2018. A total of 77 patients were included in the BEEP arm and 41 were allocated to the WBRT arm. A total of 112 patients were women. Additionally, almost all patients in each respective cohort completed study treatment (91.9% vs 97.4%). The median patient age was 56 years (range, 34-71), and most patients had a KPS of 70% or more. Over half of patients had hormone receptor–positive (62.5%) and ERBB2-positive breast cancer (54.5%).

In a subgroup analysis that assessed outcomes in patients with and without ERBB2 positivity, investigators reported a brain-specific ORR of 69.1% following BEEP compared with 84.2% in the WBRT alone cohort among those with ERBB2 positivity, as well as 59.4% vs 68.4% in the ERBB2-negative subgroup.

A total of 31.1% of patients in the BEEP cohort and 31.6% in the WBRT cohort went on to receive capecitabine and lapatinib as a subsequent treatment for BMBC. Additionally, 29.7% vs 31.6%, respectively, went on to BEEP or bevacizumab plus cisplatin or carboplatin (BP) rechallenge or treatment following WBRT. A second round of BEEP or BP were administered in 10.8% vs 15.8% of patients in each respective cohort following BMBC progression.

The majority of toxicities observed during the study were considered mild to moderate and could be managed via supportive care, including prophylactic GCSF and interrupted or modified treatment. In total, 27% of patients in the BEEP cohort and 29% in the WBRT alone cohort experienced serious adverse effects (AEs). Common AEs in the BEEP cohort included neutropenia (30.2%), nausea (27.9%), anemia (27.4%), and leukopenia (24.2%).

Reference

Chen TWW, Sai, MS, Tseng LM, et al. Whole-brain radiotherapy alone vs preceded by bevacizumab, etoposide, and cisplatin for untreated brain metastases from breast cancer. JAMA Oncol. Published online December 21, 2023. doi:10.1001/jamaoncol.2023.5456