Resistance Mutations: Next in ER+ Metastatic Breast Cancer?

“Estrogen receptor (ER) mutations can be easily detected in the plasma of patients with metastatic breast cancer and may hold the key to targeted treatments for women with endocrine-resistant disease, according to new analysis of patients in the BOLERO-2 trial.

” ‘Patients who had mutations had a shorter median survival than those who did not…and patients with different mutations might have different responses to therapies,’ Sarat Chandarlapaty, MD, PhD, a breast medical oncologist from Memorial Sloan Kettering Cancer Center in New York reported at the San Antonio Breast Cancer Symposium.

“BOLERO-2 enrolled postmenopausal women with metastatic, endocrine-resistant, ER-positive breast cancer and changed the standard of care in this setting, as reported by Medscape Medical News.”


Everolimus–Exemestane Combination Failed to Significantly Extend OS in Advanced Breast Cancer

The gist: A clinical trial with volunteer patients tested a treatment for postmenopausal women with HR-positive, HER-2–negative advanced breast cancer. The treatment combines the drugs everolimus and exemestane. The clinical trial compared it to exemestane alone. The combination did NOT appear to give longer overall survival rates than exemestane alone.

“The addition of everolimus to exemestane extended OS in postmenopausal women with HR-positive, HER-2–negative advanced breast cancer, but the difference was not statistically significant, according to results of the BOLERO-2 study.

“BOLERO-2 is a randomized phase 3, double blind, international trial.

“Prior results showed the addition of 10 mg daily everolimus (Afinitor, Novartis) — an inhibitor of mammalian target of rapamycin (mTOR) — to 25 mg daily exemestane significantly extended PFS compared with exemestane alone (7.8 months vs. 3.2 months; P<.001).

“In the current study, Martine Piccart, MD, PhD, professor of oncology at the Université Libre de Bruxelles in Belgium and director of medicine at Institut Jules Bordet, and colleagues presented OS outcomes as part of a prospectively planned secondary-endpoint analysis.

“Results showed patients assigned the combination demonstrated longer median OS (31 months vs. 26.6 months; HR=0.89; 95% CI, 0.73-1.1), but the difference was not statistically significant.

“ ‘Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting,’ Piccart and colleagues wrote.”


Everolimus Plus Exemestane Extended PFS in Invasive Lobular Carcinoma

The gist: This article discusses the results of a clinical trial—a research study with volunteer patients. The trial tested a new treatment for patients with advanced, HR-positive, HER-2-negative invasive lobular carcinoma. The new treatment combines the drugs everolimus and exemestane. The researchers found that it significantly prolonged the amount of time patients lived without their cancer worsening.

“The addition of everolimus to exemestane significantly prolonged PFS in a subset of patients with HR-positive, HER-2–negative advanced breast cancer who had invasive lobular carcinoma at baseline, according to a subanalysis of the BOLERO-2 trial presented at the Breast Cancer Symposium.

“Gabriel N. Hortobagyi, MD, FACP, professor of medicine in the department of breast medical oncology at The University of Texas MD Anderson Cancer Center, and colleagues evaluated data from 104 patients with invasive lobular carcinoma. The cohort included patients with predominantly peritoneal, gastrointestinal and ovarian metastases.

“Patients received exemestane (Aromasin, Pfizer) with everolimus (Afinitor, Novartis; n=64) or placebo (n=40).

“The median age of the patients was 63 years, and 47.1% had measurable disease. Thirty-six percent of patients had visceral metastases of the lung, liver, pleural and peritoneum; 10% had lung metastases; and 23% had liver metastases.”