依维莫司＋曲妥珠单抗＋紫杉醇用于亚洲晚期乳腺癌患者的亚组分析

　　2017年4月11日，英国《生物医学中心》旗下《乳腺癌研究》在线发表日本京都大学戸井雅和、复旦大学附属肿瘤医院邵志敏、洛杉矶加利福尼亚大学、台湾阳明大学台北荣民总医院曾令民、哈尔滨医科大学附属肿瘤医院张清媛、上海交通大学医学院附属瑞金医院沈坤炜、中山大学肿瘤防治中心刘冬耕、江苏省肿瘤医院冯继锋、中国医学科学院北京协和医学院肿瘤医院徐兵河、浙江中医药大学附属浙江省肿瘤医院王晓稼、韩国国家癌症中心、香港屯门医院吴廷英、法国诺华、瑞士诺华、军事医学科学院附属医院（北京307医院）江泽飞的探索性亚组分析报告，评价了BOLERO-1研究依维莫司治疗人表皮生长因子受体2（HER2）阳性晚期乳腺癌亚洲患者的有效性和安全性。

　　该研究入组HER2阳性晚期乳腺癌尚未接受全身治疗的绝经后女性，按2∶1随机分组接受依维莫司或安慰剂＋曲妥珠单抗＋紫杉醇。两个主要终点为全部人群和激素受体阴性亚组的研究者评定无进展生存（PFS）。次要终点包括客观反应率、临床获益率和安全性的评定。

　　结果发现：

• 亚洲患者（依维莫司组198例，安慰剂组105例）与全部患者相比，中位无进展生存相似（风险比：0.82，95%置信区间：0.61～1.11）。

• 在激素受体阴性亚组中，依维莫司与安慰剂相比，中位无进展生存延长10.97个月（25.46比14.49个月，风险比=0.48，95%置信区间：0.29～0.79）。

• 亚洲患者的依维莫司任何级别最常见不良事件为口腔炎、腹泻、皮疹、中性粒细胞减少（62.2%、48.0%、43.4%、42.3%）。

• 3、4级最常见不良事件为中性粒细胞减少（27.6%、4.6%）和中性粒细胞计数较少（11.2%、3.6%）。

• 严重不良事件包括肺实质炎、肺间质炎、间质性肺病（5.1%、3.1%、3.1%）。

• 依维莫司治疗期间死亡3例人（1.5%），安慰剂组无死亡。

　　因此，依维莫司＋曲妥珠单抗＋紫杉醇一线治疗HER2阳性晚期乳腺癌亚洲患者的有效性和安全性与既往总体患者人群报道相似。

Breast Cancer Res. 2017 Apr 11;19(1):47.

Efficacy and safety of everolimus in combination with trastuzumab and paclitaxel in Asian patients with HER2+ advanced breast cancer in BOLERO-1.

Toi M, Shao Z, Hurvitz S, Tseng LM, Zhang Q, Shen K, Liu D, Feng J, Xu B, Wang X, Lee KS, Ng TY, Ridolfi A, Noel-Baron F, Ringeisen F, Jiang Z.

Kyoto University, Sakyo-ku, Kyoto, Japan; Cancer Hospital of Fudan University, Shanghai, China; University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Taipei Veterans General Hospital, National Yang Ming University, Taipei, Taiwan; Tumor Hospital of Harbin Medical University, Harbin, China; Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China; Sun Yat-sen University Cancer Center, Guangzhou, China; Jiangsu Cancer Hospital, 210009, Nanjing, China; Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Affiliated Zhejiang Cancer Hospital of Zhejiang Chinese Medical University Hangzhou, Hangzhou, Zhejiang Province, China; Center for Breast Cancer, National Cancer Center, Gyeunggi-do, South Korea; Tuen Mun Hospital, Tuen Mun, Hong Kong; Novartis Pharma SAS, Rueil-Malmaison, France; Novartis Pharma AG, Basel, Switzerland; Beijing 307 Hospital of PLA, Beijing, China.

BACKGROUND: The current exploratory analysis was performed to evaluate the efficacy and safety of everolimus for treatment of human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer in the Asian subset of patients in the BOLERO-1 trial.

METHODS: Postmenopausal women with HER2+ advanced breast cancer, who had not received systemic therapy for advanced disease, were randomized 2:1 to receive everolimus or placebo, plus trastuzumab and paclitaxel. The two primary end points were investigator-assessed progression-free survival (PFS) in the full population and in the hormone receptor-negative (HR-) subpopulation. Secondary end points included assessment of the objective response rate, the clinical benefit rate, and safety.

RESULTS: In the Asian subset, median PFS was similar in the everolimus (n = 198) and placebo (n = 105) arms in the full analysis set (hazard ratio = 0.82 (95% CI 0.61-1.11)). In the HR- subpopulation, everolimus prolonged median PFS by 10.97 months vs placebo (25.46 vs 14.49 months; hazard ratio = 0.48 (95% CI 0.29-0.79)). In the everolimus arm of the Asian subset, the most common adverse events of any grade were stomatitis (62.2%), diarrhea (48.0%), rash (43.4%) and neutropenia (42.3%). Neutropenia (grade 3: 27.6%; grade 4: 4.6%) and decreased neutrophil count (grade 3: 11.2%; grade 4: 3.6%) were the most frequent grade 3/4 adverse events. Serious adverse events included pneumonia (5.1%), pneumonitis (3.1%), and interstitial lung disease (3.1%). There were three deaths (1.5%) during treatment in the everolimus arm vs none in the placebo arm.

CONCLUSIONS: The efficacy and safety of everolimus plus trastuzumab and paclitaxel as first-line treatment for HER2+ advanced breast cancer in the Asian subset was consistent with that reported previously in the overall population.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT00876395

KEYWORDS: Advanced breast cancer; Asian; BOLERO-1; Everolimus; HER2; Metastatic breast cancer

PMID: 28399902

DOI: 10.1186/s13058-017-0839-0