Randomized phase II comparison of single-agent carboplatin versus combination of carboplatin and everolimus for advanced triple negative breast cancer

Purpose: Triple-negative breast cancers (TNBCs) are associated with a high frequency of PTEN loss, which can lead to activation of the mTOR pathway and tumor proliferation but may be reversible with the mTOR inhibitor everolimus. A prior phase II single-arm trial of carboplatin and everolimus in patients with advanced TNBC demonstrated good tolerability and preliminary efficacy. Patients and methods: A phase II randomized trial in patients with advanced TNBC, with 0–3 prior lines of therapy, was conducted. Patients were randomized 2:1 to receive carboplatin and everolimus or carboplatin alone. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and safety. Results: Between 2015 and 2022, 59 patients were randomized to carboplatin/everolimus (n = 38) or carboplatin alone (n = 21). The median age of the population was 62 years and 68% had received at least one prior line of therapy. Median PFS was significantly improved in patients who received carboplatin/everolimus (4.7 months) versus carboplatin alone (4.2 months; HR:0.49; 95% CI: 0.25–0.98; p = 0.0390). OS was 17.6 months with the combination and 14.6 months with carboplatin alone (HR:1.17; 95% CI: 0.59–2.30; p = 0.6593). The most common adverse events (AEs) on the combination included thrombocytopenia, anemia, leukopenia, and neutropenia. Conclusion: The combination of carboplatin and everolimus in this study reduced the risk of progression or death by 52%. The regimen was well tolerated and provides a promising treatment option for patients with advanced TNBC.