Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study.
Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study.
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DOI：
10.1007/s10549-017-4537-5
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发表时间：
2018-03
影响因子：
3.8
通讯作者：
Hamilton EP
中科院分区：
文献类型：
--
作者：
Dirix LY;Takacs I;Jerusalem G;Nikolinakos P;Arkenau HT;Forero-Torres A;Boccia R;Lippman ME;Somer R;Smakal M;Emens LA;Hrinczenko B;Edenfield W;Gurtler J;von Heydebreck A;Grote HJ;Chin K;Hamilton EP
靶向程序性死亡受体1（PD-1）或其配体（PD-L1）的药物在治疗转移性乳腺癌（MBC）中显示出抗肿瘤活性。本研究的目的是评估avelumab（一种PD-L1抑制剂）在MBC患者中的活性。在一项I期试验（JAVELIN实体瘤; NCT 01772004）中，标准治疗难治或治疗后进展的MBC患者接受avelumab 10 mg/kg静脉给药，每2周一次。根据RECIST v1.1，每6周评估一次肿瘤。按照NCI-CTCAE v4.0对不良事件（AE）进行分级。通过免疫组织化学法（Dako PD-L1 IHC 73-10 pharmDx）评估膜PD-L1表达。共有168例MBC患者，包括58例三阴性乳腺癌（TNBC）患者，接受avelumab治疗2-50周，随访6-15个月。患者接受了中位3种既往转移性或局部晚期疾病治疗的重度预治疗。13.7%的患者发生了≥ 3级治疗相关AE，包括2例治疗相关死亡。总体确认的客观缓解率（ORR）为3.0%（1例完全缓解和4例部分缓解），TNBC患者为5.2%。在总体人群（16.7% vs. 1.6%）和TNBC亚组（22.2% vs. 2.6%）中，与PD-L1−肿瘤相关免疫细胞患者相比，在PD-L1+患者中观察到ORR更高的趋势。Avelumab在MBC患者亚组中显示出可接受的安全性特征和临床活性。肿瘤相关免疫细胞中的PD-L1表达可能与MBC患者对avelumab产生临床应答的概率较高相关。
Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2–50 weeks and followed for 6–15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1− tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
45.3
作者：
Nanda, Rita;Chow, Laura Q. M.;Buisseret, Laurence
通讯作者：
Buisseret, Laurence
影响因子：
50.5
作者：
Andre, F.;Zielinski, C. C.
通讯作者：
Zielinski, C. C.
DOI：
10.1016/s1470-2045(16)30364-3
发表时间：
2016-10
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Kaufman HL;Russell J;Hamid O;Bhatia S;Terheyden P;D'Angelo SP;Shih KC;Lebbé C;Linette GP;Milella M;Brownell I;Lewis KD;Lorch JH;Chin K;Mahnke L;von Heydebreck A;Cuillerot JM;Nghiem P
通讯作者：
Nghiem P
影响因子：
5.8
作者：
Grenga I;Donahue RN;Lepone LM;Richards J;Schlom J
通讯作者：
Schlom J