帕博利珠单药对三阴性乳腺癌有效
对于既往治疗失败的转移性三阴性乳腺癌，治疗选择有限。多中心非随机IB期研究KEYNOTE-012已经证实了细胞程序性死亡蛋白-1（PD-1）免疫检查点抑制剂帕博利珠单抗对进展期三阴性乳腺癌患者的安全性和抗肿瘤活性。
2018年11月26日，欧洲肿瘤内科学会《肿瘤学报》在线发表美国默沙东、纽约大学、旧金山加利福尼亚大学、哈佛大学达纳法伯癌症研究所、芝加哥大学、罗格斯大学、贝勒大学、莱文癌症研究所、英国伦敦玛丽王后大学、法国西部癌症研究所、巴黎居里研究所、比利时布鲁塞尔自由大学、加拿大多伦多大学、日本爱知癌症中心、澳大利亚悉尼大学、墨尔本大学、意大利米兰大学、以色列特拉维夫大学、西班牙巴塞罗那大学、马德里大学的II期KEYNOTE-086研究A组报告，评估了帕博利珠单抗单药对既往治疗失败转移性三阴性乳腺癌的有效性和安全性。
该研究入组曾经接受转移病变全身治疗失败至少一次、既往任何疾病分期使用过蒽环类和紫杉类治疗并且最近一次治疗期间或之后发生进展的集中确诊转移性三阴性乳腺癌女性患者170例，其中PD-L1阳性患者占61.8%，曾经接受转移病变全身治疗至少失败三次占43.5%。患者接受每3周静脉注射帕博利珠单抗200毫克连续2年，主要终点为所有患者和PD-L1阳性患者的客观缓解率和安全性。次要终点包括缓解维持期、疾病控制率（完全或部分缓解或疾病稳定≥24周的患者百分比）、无进展生存和总生存。
结果，所有患者、PD-L1阳性患者：
客观缓解率分别为5.3%、5.7%（95%置信区间：2.7～9.9、2.4～12.2）
疾病控制率分别为7.6%、9.5%（95%置信区间：4.4～12.7、5.1～16.8）
缓解维持期分别为1.2～21.5、6.3～21.5个月（尚未达到中位）
中位无进展生存期为2.0个月（95%置信区间：1.9～2.0），6个月无进展生存率为14.9%。中位总生存期为9.0个月（95%置信区间：7.7～11.2），6个月总生存率为69.1%。
治疗相关不良事件103例（60.6%），其中3～4级不良事件22例（12.9%），无不良事件所致死亡。
因此，该研究结果表明，对于既往治疗失败的转移性三阴性乳腺癌患者，帕博利珠单抗单药有效，并且安全性可控。
相关阅读
Ann Oncol. 2018 Nov 26. [Epub ahead of print]
Pembrolizumab Monotherapy for Previously Treated Metastatic Triple-Negative Breast Cancer: Cohort A of the Phase 2 KEYNOTE-086 Study.
S Adams, P Schmid, H S Rugo, E P Winer, D Loirat, A Awada, D W Cescon, H Iwata, M Campone, R Nanda, R Hui, G Curigliano, D Toppmeyer, J O'Shaughnessy, S Loi, S Paluch-Shimon, A R Tan, D Card, J Zhao, V Karantza, J Cortés.
Perlmutter Cancer Center, New York University School of Medicine, New York, NY, USA; Centre for Experimental Cancer Medicine, Barts Cancer Institute, London, UK; University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA; Dana-Farber Cancer Institute, Boston, MA, USA; Institut Curie, Paris, France; Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium; Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada; Aichi Cancer Center Hospital, Nagoya, Japan; Institut de Cancerologie de l'Ouest, Nantes, France; The University of Chicago, Chicago, IL, USA; Westmead Hospital and the University of Sydney, Sydney, NSW, Australia; University of Milano, Istituto Europeo di Oncologia, Milan, Italy; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA; Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, USA; Peter MacCallum Cancer Centre, Melbourne, Australia; Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Levine Cancer Institute, Atrium Health, Charlotte, NC, USA; Merck & Co., Inc., Kenilworth, NJ, USA; Vall d'Hebron Institute of Oncology, Barcelona, Spain; Ramon y Cajal University Hospital, Madrid, Spain; Institute of Oncology, Quiron Group, Barcelona, Spain.
BACKGROUND: Treatment options for previously treated metastatic triple-negative breast cancer (mTNBC) are limited. In cohort A of the phase 2 KEYNOTE-086 study, we evaluated pembrolizumab as second or later line of treatment for patients with mTNBC.
PATIENTS AND METHODS: Eligible patients had centrally confirmed mTNBC, ≥1 systemic therapy for metastatic disease, prior treatment with anthracycline and taxane in any disease setting, and progression on or after the most recent therapy. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. Primary endpoints were objective response rate (ORR) in the total and PD-L1-positive populations, and safety. Secondary endpoints included duration of response, disease control rate (DCR; percentage of patients with complete or partial response or stable disease for ≥24 weeks), progression-free survival (PFS), and overall survival (OS).
RESULTS: All enrolled patients (N=170) were women, 61.8% had PD-L1-positive tumors, and 43.5% had received ≥3 previous lines of therapy for metastatic disease. ORR (95% CI) was 5.3% (2.7-9.9) in the total and 5.7% (2.4-12.2) in the PD-L1-positive populations. DCR (95% CI) was 7.6% (4.4-12.7) and 9.5% (5.1-16.8), respectively. Median duration of response was not reached in the total (range, 1.2+-21.5+) and in the PD-L1-positive (range, 6.3-21.5+) populations. Median PFS was 2.0 months (95% CI, 1.9-2.0), and the 6-month rate was 14.9%. Median OS was 9.0 months (95% CI, 7.7-11.2), and the 6-month rate was 69.1%. Treatment-related adverse events (AEs) occurred in 103 (60.6%) patients, including 22 (12.9%) with grade 3 or 4 AEs. There were no deaths due to AEs.
CONCLUSIONS: Pembrolizumab monotherapy demonstrated durable antitumor activity in a subset of patients with previously treated mTNBC and had a manageable safety profile.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02447003
DOI: 10.1093/annonc/mdy517
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