帕博利珠单抗单药治疗既往治疗的转移性三阴性乳腺癌：KEYNOTE-086 研究的 2 期队列 A。

Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study.

机构信息

Department of Medicine, Perlmutter Cancer Center, New York University School of Medicine, New York, USA.

Centre for Experimental Cancer Medicin, Barts Cancer Institute, Queen Mary University London, London, UK.

出版信息

Ann Oncol. 2019 Mar 1;30(3):397-404. doi: 10.1093/annonc/mdy517.

DOI:10.1093/annonc/mdy517

PMID:30475950

Abstract

BACKGROUND

Treatment options for previously treated metastatic triple-negative breast cancer (mTNBC) are limited. In cohort A of the phase II 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 end points were objective response rate in the total and PD-L1-positive populations, and safety. Secondary end points included duration of response, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), progression-free survival, and overall survival.

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. Disease control rate (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, 7.6-11.2), and the 6-month rate was 69.1%. Treatment-related adverse events 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.

摘要

背景

先前治疗的转移性三阴性乳腺癌（mTNBC）的治疗选择有限。在 II 期 KEYNOTE-086 研究的队列 A 中，我们评估了 pembrolizumab 作为 mTNBC 的二线或后线治疗。

患者和方法

符合条件的患者经中心确认患有 mTNBC，转移性疾病有≥1 种全身治疗，既往在任何疾病背景下接受过蒽环类药物和紫杉烷治疗，且在最近一次治疗后出现进展。患者接受 pembrolizumab 200mg 静脉注射，每 3 周一次，最长 2 年。主要终点为总人群和 PD-L1 阳性人群的客观缓解率，以及安全性。次要终点包括缓解持续时间、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）、无进展生存期和总生存期。

结果

所有入组患者（n=170）均为女性，61.8%的肿瘤为 PD-L1 阳性，43.5%的患者在转移性疾病中接受了≥3 线的治疗。总人群和 PD-L1 阳性人群的客观缓解率（95%CI）分别为 5.3%（2.7-9.9）和 5.7%（2.4-12.2）。疾病控制率（95%CI）分别为 7.6%（4.4-12.7）和 9.5%（5.1-16.8）。总人群和 PD-L1 阳性人群的中位缓解持续时间均未达到（范围，1.2+-21.5+和 6.3-21.5+）。中位无进展生存期为 2.0 个月（95%CI，1.9-2.0），6 个月时的缓解率为 14.9%。中位总生存期为 9.0 个月（95%CI，7.6-11.2），6 个月时的生存率为 69.1%。103 例（60.6%）患者发生治疗相关不良事件，包括 22 例（12.9%）发生 3 级或 4 级不良事件。无治疗相关死亡事件。