Everolimus plus aromatase inhibitors as maintenance therapy after first-line chemotherapy: Final results of the phase III randomised MAIN-A (MAINtenance Afinitor) trial

Abstract

Background: Despite endocrine therapy being the mainstay of treatment for hormone receptor positive (HRþ)/HER2À metastatic breast cancer, patients at risk of visceral crisis or doubt for endocrine sensitivity are still offered first-line chemotherapy. Maintenance hormonal therapy is generally offered at the discontinuation of chemotherapy. The MAINtenance Afinitor study is a randomised, phase III trial comparing maintenance everolimus combined with aromatase inhibitors (AIs) versus AI monotherapy in patients with disease control after first-line chemotherapy. Methods: Patients with stable disease, partial response or complete response after first-line chemotherapy were randomised to everolimus plus AIs (exemestane or letrozole or anastrozole) or to AIs alone. Primary aim was progression-free survival (PFS). Secondary aims included response rate, safety and overall survival (OS). Results: In total, 110 patients were randomised to everolimus þ AIs (n Z 52) or to AIs (n Z 58). Median PFS was 11.0 months (95% confidence interval [CI] 8.1e13.8) in the everolimus þ AI arm and 7.2 months (95% CI 4.7e10.9) in the AI monotherapy arm (hazard ra t i o [ HR ] 0. 7 1, 9 5 % C I 0 . 4 7 e1.06). Objective response r ate w as 22.4% in everolimus þ AI arm and 19.2% in AI monotherapy arm. A higher proportion of disease progression as best response was reported in the AI monotherapy arm (28.8% versus 14.3%). Median OS was 35.7 months (95% CI 26.0e47.8) in the combination arm versus 33.5 (95% CI 26.4e42.7) in the AI alone arm (HR 1.0, 95% CI 0.61e1.62). Conclusions: EVE þ AIs did not significantly impact on the outcome of metastatic breast cancer patients deemed suitable for first-line chemotherapy. Also taking into account treatment tolerability, maintenance endocrine therapy remains the standard.

Major advancements in metastatic breast cancer treatment: when expanding options means prolonging survival

“…In this context, type and duration of first-line chemotherapy have not been well established; however, depending on timing/magnitude of response as well as tolerability, switch to maintenance endocrine therapy (ET) is generally considered with the aim of delaying disease progression. 37 , 38 …”

Anti-hormonal maintenance treatment with the CDK4/6 inhibitor ribociclib after 1st line chemotherapy in hormone receptor positive / HER2 negative metastatic breast cancer: A phase II trial (AMICA)

“…To improve the efficacy of maintenance treatment, the phase III MAIN-A study compared maintenance everolimus combined with aromatase inhibitors (AI) versus AI monotherapy in patients with disease control after the first palliative chemotherapy [ 23 ]. As median PFS with 11.0 months versus 7.2 months (hazard ratio 0.71, [95% CI 0.47–1.06]) was not significantly improved and considering the substantial toxicities, the authors concluded that such a treatment strategy is not warranted.…”

Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK)

“…Similarly, everolimus combined with an aromatase inhibitor (AI) has shown promising therapeutic activity in patients suffering from breast cancer. The median PFS in the everolimus plus AI group and the AI monotherapy group was 11.0 months and 7.2 months respectively, with ORRs of 22.4% and 19.2% respectively 227 . When everolimus was combined with bevacizumab to treat patients with the RCC form of metastatic cancer, the median PFS was 13.7 months with an ORR of 35%.…”