2016年5月2日，美国临床肿瘤学会（ASCO）官方期刊《临床肿瘤学杂志》（JCO）在线发表了芝加哥大学、华盛顿大学、北卡罗来纳大学、H.李·莫菲特癌症中心和研究所、耶鲁大学医学院、默克公司、以色列希巴医疗中心、特拉维夫索拉斯基医疗中心、比利时布鲁塞尔自由大学的多中心非随机ⅠB期研究（KEYNOTE-012），评估了程序性细胞死亡蛋白质1（PD-1）抑制剂培布利珠单抗用于进展期三阴性乳腺癌患者的安全性和抗肿瘤活性。
该研究发现111例三阴性乳腺癌患者中有58.6%的PD-L1阳性，32例患者（中位年龄50.5岁）最终进入安全性和抗肿瘤活性评估。平均接受培布利珠单抗（每2周静脉注射10mg/kg）治疗5个周期，治疗的常见不良反应包括关节痛，疲劳，肌痛，恶心等，5例患者出现≥3级不良反应，1例出现治疗相关死亡。进入抗肿瘤活性评估的27例患者，治疗总缓解率为18.5%（5/27），实现缓解的中位时间为18周（范围：7.3～32.4周），中位缓解持续时间尚未达到。
该ⅠB期研究是培布利珠单抗治疗三阴性乳腺癌的初步数据，显示了临床活性和可接受的安全性。每3周注射200mg的单药Ⅱ期研究正在进行中。
J Clin Oncol. 2016 May 2. [Epub ahead of print]
Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study.
Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L.
University of Chicago, Chicago, IL.
University of Washington, Seattle, WA.
University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC.
Sheba Medical Center, Tel Hashomer.
Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
Yale University School of Medicine, New Haven, CT.
Merck & Co., Kenilworth, NJ.
Université Libre de Bruxelles, Bruxelles, Belgium.
PURPOSE: Immune checkpoint inhibition has been demonstrated to be an effective anticancer strategy. Several lines of evidence support the study of immunotherapy in triple-negative breast cancer (TNBC). We assessed the safety and antitumor activity of the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab in patients with advanced TNBC.
METHODS: KEYNOTE-012 (ClinicalTrials.gov identifier: NCT01848834) was a multicenter, nonrandomized phase Ib trial of single-agent pembrolizumab given intravenously at 10 mg/kg every 2 weeks to patients with advanced PD-L1-positive (expression in stroma or ≥ 1% of tumor cells by immunohistochemistry) TNBC, gastric cancer, urothelial cancer, and head and neck cancer. This report focuses on the TNBC cohort.
RESULTS: Among 111 patients with TNBC whose tumor samples were screened for PD-L1 expression, 58.6% had PD-L1-positive tumors. Thirty-two women (median age, 50.5 years; range, 29 to 72 years) were enrolled and assessed for safety and antitumor activity. The median number of doses administered was five (range, 1 to 36 doses). Common toxicities were mild and similar to those observed in other tumor cohorts (eg, arthralgia, fatigue, myalgia, and nausea), and included five (15.6%) patients with grade ≥ 3 toxicity and one treatment-related death. Among the 27 patients who were evaluable for antitumor activity, the overall response rate was 18.5%, the median time to response was 17.9 weeks (range, 7.3 to 32.4 weeks), and the median duration of response was not yet reached (range, 15.0 to ≥ 47.3 weeks).
CONCLUSION: This phase Ib study describes preliminary evidence of clinical activity and a potentially acceptable safety profile of pembrolizumab given every 2 weeks to patients with heavily pretreated, advanced TNBC. A single-agent phase II study examining a 200-mg dose given once every 3 weeks (ClinicalTrials.gov identifier: NCT02447003) is ongoing.
PMID: 27138582
PII: JCO648931
DOI: 10.1200/JCO.2015.64.8931
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