Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study
Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study
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DOI：
10.1093/annonc/mdy518
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发表时间：
2019-03-01
影响因子：
50.5
通讯作者：
Cortes, J.
中科院分区：
文献类型：
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作者：
Adams, S.;Schmid, P.;Cortes, J.
转移性三阴性乳腺癌（mTNBC）的标准一线治疗是化疗。然而，结果很差，需要新的治疗方案。在KEYNOTE-086 II期研究的B队列中，我们评估了派姆单抗作为pd - l1阳性mTNBC患者的一线治疗。患者和方法符合条件的患者为中央确诊的mTNBC，既往未接受过转移性疾病的全身抗癌治疗，根据中央复查RECIST v1.1可测量的基线疾病，无中枢神经系统转移的影像学证据，肿瘤PD-L1联合阳性评分为1。患者每3周静脉注射200mg派姆单抗，疗程长达2年。主要终点是安全性。次要终点包括客观缓解率、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）、缓解持续时间、无进展生存期和总生存期。结果84例患者均为女性，其中73例（86.9%）接受过辅助治疗。53例（63.1%）患者出现治疗相关不良事件（ae），其中8例（9.5%）严重程度为3级；没有患者发生4级不良事件或因治疗相关不良事件死亡。4例患者完全缓解，14例患者部分缓解，客观缓解率为21.4% （95% CI 13.9-31.4）。13例病情稳定的患者中，2例病情稳定持续24周，疾病控制率为23.8% （95% CI 15.9 ~ 34.0）。截止数据时，18例缓解中有8例（44.4%）正在进行中，中位缓解持续时间为10.4个月（范围4.2至19.2+）。中位无进展生存期为2.1个月（95% CI 2.0-2.2），中位总生存期为18.0个月（95% CI 12.9-23.0）。结论：Pembrolizumab单药治疗具有可控的安全性，并且作为pd - l1阳性mTNBC患者的一线治疗具有持久的抗肿瘤活性。临床试验注册：ClinicalTrials.gov, NCT02447003。背景：先前治疗过的转移性三阴性乳腺癌（mTNBC）的治疗选择是有限的。在KEYNOTE-086 II期研究的A队列中，我们评估了派姆单抗作为mTNBC患者的二线或二线治疗。患者和方法符合条件的患者有中央确诊的mTNBC， 1次转移性疾病的全身治疗，之前在任何疾病情况下接受过蒽环类药物和紫杉烷治疗，并且在最近的治疗中或之后有进展。患者每3周静脉注射200mg派姆单抗，疗程长达2年。主要终点是总人群和pd - l1阳性人群的客观缓解率和安全性。次要终点包括反应持续时间、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%为pd - l1阳性肿瘤，43.5%既往接受过3次转移性疾病治疗。总体的ORR （95% CI）为5.3% (2.7-9.9)，pd - l1阳性人群的ORR为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（1.2+-21.5+）和pd - l1阳性人群（6.3-21.5+）的中位反应持续时间未达到。中位PFS为2.0个月（95% CI, 1.9-2.0）， 6个月生存率为14.9%。中位OS为9.0个月（95% CI, 7.6-11.2）， 6个月生存率为69.1%。103例（60.6%）患者发生治疗相关不良事件，其中22例（12.9%）为3级或4级ae。没有因ae而死亡的病例。结论：Pembrolizumab单药治疗在先前治疗过的mTNBC患者中显示出持久的抗肿瘤活性，并且具有可管理的安全性。临床试验注册：ClinicalTrials.gov, NCT02447003
Background Standard first-line treatment of metastatic triple-negative breast cancer (mTNBC) is chemotherapy. However, outcomes are poor, and new treatment options are needed. In cohort B of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as first-line therapy for patients with PD-L1-positive mTNBC.Patients and methods Eligible patients had centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, measurable disease at baseline per RECIST v1.1 by central review, no radiographic evidence of central nervous system metastases, and a tumor PD-L1 combined positive score 1. Patients received pembrolizumab 200mg intravenously every 3weeks for up to 2years. The primary end point was safety. Secondary end points included objective response rate, disease control rate (percentage of patients with complete or partial response or stable disease for 24weeks), duration of response, progression-free survival and overall survival.Results All 84 patients enrolled were women, and 73 (86.9%) received prior (neo)adjuvant therapy. Fifty-three (63.1%) patients had treatment-related adverse events (AEs), including 8 patients (9.5%) with grade 3 severity; no patients experienced grade 4 AEs or died because of treatment-related AEs. Four patients had a complete response and 14 had a partial response, for an objective response rate of 21.4% (95% CI 13.9-31.4). Of the 13 patients with stable disease, 2 had stable disease lasting 24weeks, for a disease control rate of 23.8% (95% CI 15.9-34.0). At data cut-off, 8 of 18 (44.4%) responses were ongoing, and median duration of response was 10.4months (range 4.2 to 19.2+). Median progression-free survival was 2.1months (95% CI 2.0-2.2), and median overall survival was 18.0months (95% CI 12.9-23.0).Conclusions Pembrolizumab monotherapy had a manageable safety profile and showed durable antitumor activity as first-line therapy for patients with PD-L1-positive mTNBC.Clinical trial registration ClinicalTrials.gov, NCT02447003.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 200mg intravenously every 3weeks for up to 2years. 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 24weeks), 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 2.0months (95% CI, 1.9-2.0), and the 6-month rate was 14.9%. Median OS was 9.0months (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