エキセメスタンとエベロリムス併用の有効性が確認された（Abstract # S3-7）

BOLERO-2：エキセメスタンとエベロリムスの併用により転移性乳がん女性の無増悪生存期間が上昇した
BOLERO-2: Exemestane plus everolimus increased progression-free survival for women with metastatic breast cancer
ホルモン受容体（HR）陽性の転移性乳がんを有する閉経後女性に対し、エベロリムスとエキセメスタンの併用は疾患コントロール期間を著明に改善したとの、phase3臨床試験、経口エベロリムス乳がんトライアル（Breast Cancer Trials of Oral Everolimus [BOLERO-2]）の結果が2011年CTRC-AACRサンアントニオ乳がんシンポジウムで発表された。研究者らはHR陽性転移性乳がんを有しアナストロゾールまたはレトロゾール投与中に疾患が進行した閉経後女性724人を組み入れた。患者はエキセメスタンとエベロリムスの併用療法またはエキセメスタンとプラセボを投与する群に無作為に割り付けられた。その結果、エキセメスタンとプラセボを投与された患者239人の無増悪生存期間中央値は3.2ヵ月であった。エキセマスタンとエベロリムスの併用療法を受けた患者485人においては、無増悪生存期間中央値は7.4ヵ月と有意であった。完全寛解、部分寛解、または6ヵ月を超える疾患の安定などの臨床有効率は、エキセメスタンとプラセボを投与した患者の25.5%に認められたのに対し、エキセメスタンとエベロリムスの併用療法群では50.5%であった。BOLERO-2の生存期間に関する解析はまだできていない。しかし、治療の忍容性は良好であり、最も多い副作用は口腔粘膜炎、倦怠感、肺炎および高血糖であった。
Full Text

Everolimus in combination with exemestane has shown promise for the treatment of breast cancer.

"For postmenopausal patients with hormone receptor (HR)-positive metastatic breast cancer, the addition of everolimus to exemestane markedly improves the duration of disease control," said Gabriel N. Hortobagyi, M.D., FACP, professor of medicine, chair of the department of breast medical oncology and director of the Multidisciplinary Breast Cancer Research Program at the University of Texas MD Anderson Cancer Center in Houston.

Hortobagyi presented findings from Breast Cancer Trials of Oral Everolimus (BOLERO-2), a phase 3 clinical trial, at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.

BOLERO-2 researchers enrolled 724 postmenopausal patients with HR-positive metastatic breast cancer and evidence of progressive disease while receiving anastrozole or letrozole. They randomly assigned patients to treatment with exemestane plus everolimus or with exemestane plus placebo.

Results revealed a median progression-free interval of 3.2 months for 239 patients treated with exemestane plus placebo. Among the 485 patients treated with exemestane plus everolimus, researchers found a median progression-free interval of 7.4 months, "a highly significant difference," Hortobagyi said.

Clinical benefit rates, which include complete response, partial response, or stable disease exceeding six months, were 25.5 percent among patients treated with exemestane and placebo and 50.5 percent among those treated with exemestane and everolimus.

"The original hypothesis predicted this increased benefit from the combination, based on compelling preclinical experiments and preliminary results from earlier, smaller clinical trials. These results establish a new standard of care for this group of patients," Hortobagyi said.

He continued, "These results highlight the progress being made in understanding the evolving mechanisms of resistance to standard therapies."

Researchers were not yet able to measure survival analysis in BOLERO-2. However, treatment was well tolerated, with oral mucositis, fatigue, pneumonitis and hyperglycemia being the most common side effects.