The addition of everolimus to standard carboplatin chemotherapy led to a 52% reduction in the risk of disease progression or death compared with carboplatin alone in patients with advanced triple-negative breast cancer, according to the results of a randomized phase II trial published in Breast Cancer Research and Treatment.
“Triple-negative breast cancer has limited treatment options and is often resistant to standard therapies,” said senior study author Amy Tiersten, MD, Professor of Medicine (Hematology and Medical Oncology) at the Icahn School of Medicine. “Our findings suggest that the combination of carboplatin and everolimus could offer a new option for patients, and should be further tested in larger clinical trials to confirm its effectiveness and safety.”
Background and Study Methods
Triple-negative breast cancers often exhibit PTEN loss, which leads to activation of the mTOR pathway and tumor proliferation. As such, researchers have considered whether the addition of the mTOR inhibitor everolimus to standard therapy could reverse this activation and improve patient outcomes.
In a prior phase II single-arm trial of the combination of carboplatin and everolimus in patients with advanced triple-negative breast cancer showed preliminary efficacy.
Patel et al conducted a randomized phase II study of patients with advanced triple-negative breast cancer who had received up to 3 prior lines of treatment. Participating patients (n = 59) were randomly assigned 2:1 to receive either carboplatin and everolimus or carboplatin monotherapy.
Key Study Findings
The median progression-free survival was 4.7 months with the combination of carboplatin and everolimus compared with 4.2 months with carboplatin alone (hazard ratio [HR] = 0.49; 95% confidence interval [CI] = 0.25–0.98; P = .0390). The median overall survival was 17.6 months with the combination vs 14.6 months with carboplatin monotherapy (HR = 1.17; 95% CI = 0.59–2.30; P = .6593).
The most common adverse events with the combination regimen were thrombocytopenia, anemia, leukopenia, and neutropenia.
“This combination could represent a promising new treatment option for advanced triple-negative breast cancer if validated in phase III trials,” said lead study author Rima Patel, MD, Assistant Professor of Medicine (Hematology and Medical Oncology) at the Icahn School of Medicine, nothing that the efficacy of the regimen requires further study.
Disclosure: For full disclosures of the study authors, visit link.springer.com.