Maintenance Therapy with Everolimus plus Aromatase Inhibitors in Hormone Receptor–Positive, HER2-Negative Metastatic Breast Cancer: Updated Analyses of the Phase 3 Randomized MAIN-A Trial

Adopting a maintenance program of everolimus combined with aromatase inhibitors, outcomes were not improved in patients with metastatic breast cancer who were deemed possible candidates for first-line chemotherapy.

Although the mainstay of treatment for hormone receptor–positive, HER2-negative metastatic breast cancer has been endocrine therapy, first-line chemotherapy is still offered to those patients who have a high disease burden or are at risk for visceral crisis. Chemotherapy is usually followed by hormonal therapy as part of a maintenance program. In an investigator-driven, randomized, phase 3 trial called the MAIN-A study, maintenance everolimus combined with aromatase inhibitors was compared with aromatase inhibitors alone in patients with disease control after first-line chemotherapy.

Patients who were postmenopausal and succeeded at achieving stable disease, partial response, or complete disease control after receiving first-line chemotherapy were randomized to receive everolimus 10 mg daily orally plus aromatase inhibitors or aromatase inhibitors alone. The primary goal was progression-free survival (PFS), previously reported as 9.9 months versus 7.2 months (hazard ratio [HR], 0.764; 95% confidence interval [CI], 0.501-1.164) for everolimus plus aromatase inhibitors and aromatase inhibitors alone, respectively.

Valentina Guarneri, MD, PhD, Associate Professor, Oncology, University of Padua, Italy, and colleagues presented the latest data on the impact of tumor characteristics on PFS and impact on overall survival (OS). Patients (N = 110) were randomized to receive everolimus combined with aromatase inhibitors (N = 52) or aromatase inhibitors (N = 58).

In this study, patients living with visceral metastases tended to experience shorter PFS when compared with patients with soft tissues/bone metastases (median 11.1 months compared with 6.4 months; P = .0746). Interestingly, what did not impact PFS in the overall or treatment arm was the level of estrogen receptor expression. At the point when the abstract was written, the researchers noted that there were 61 recorded deaths. When comparing the 2 arms, no difference in OS was observed (median 33.9 months for everolimus plus aromatase inhibitor vs 33.5 months for aromatase inhibitor therapy; HR, 0.97; 95% CI, 0.59-1.61). By adopting a maintenance program of everolimus combined with aromatase inhibitors, metastatic breast cancer outcomes were not improved in patients who were deemed possible candidates for first-line chemotherapy.

Source: Guarneri V, Cinieri S, Dieci MV, et al. Maintenance therapy with everolimus plus aromatase inhibitors vs aromatase inhibitors as after first-line chemotherapy in HR+/HER2- metastatic breast cancer: updated analyses of the phase III randomized MAIN-A trial. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PS12-22.