(CHICAGO, IL) – Adding bevacizumab to etoposide and cisplatin therapy (BEEP) is associated with significant anti-tumor effects in breast cancer patients with brain metastases after whole-brain radiotherapy, according to an early report from a multicenter phase 2 study presented at the 2012 American Society of Clinical Oncology Annual Meeting.
With improving survival rates, brain metastasis is becoming an increasingly common complication of breast cancer, but its management remains “a severe challenge,” said lead author Yen-Shen Lu, MD, PhD, Adjunct Associate Professor, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Dr. Lu and colleagues sought to determine whether or not bevacizumab improves delivery of etoposide and cisplatin, two cytotoxic agents that have exhibited moderate activity against metastatic brain tumors from breast cancer. The primary endpoint was a centrally assessed CNS objective response (CNS-OR) defined as a ≥50% reduction in the volumetric sum of all measurable CNS lesions in the absence of increasing steroid use, development of a new CNS lesion, or progressive neurologic symptoms. Breast cancer patients with brain metastasis progression following whole brain radiotherapy were enrolled to receive a BEEP-regimen: bevacizumab (15mg/kg on Day 1; etoposide 70mg/m2/day for Days 2-4; cisplatin 70mg/m2/day on Day 2) every 21 days for up to six cycles.
Median progression-free survival (PFS) was 6.6 months; CNS PFS was 7.3 months. Nine of 12 patients (75%) achieved the primary endpoint of CNS-OR. Six patients (50%) had ≥80% reductions in tumor volumetric reduction and 3 patients (25%) had 50-80% reductions. The median treatment cycle was 4.5. Grade 4 toxicities included neutropenia (35.3%), leukopenia (11.8%), and thrombocytopenia (5.9%). Doses for seven patients (58.3%) were reduced to etoposide 60mg/m2 and cisplatin 60mg/m2.
“Since most of the patients are heavily pretreated with multiple lines of chemotherapies, high incidence of neutropenia/leukopenia adverse events was noted,” Dr. Lu said. “However, this side effect is generally manageable, and should be preventable if use of prophylaxis G-CSF is incorporated into the protocol.”
“Two patients had non-CNS disease progression while CNS tumors remained under control,” Dr. Lu said. He added that this regimen has a significant anti-tumor effect for brain metastases of breast cancer which progresses after whole brain radiotherapy.