尼伏鲁单抗联合艾瑞布林治疗 HER2 阴性转移性乳腺癌的临床活性：一项 Ib/II 期研究（KCSG BR18-16）。

Clinical activity of nivolumab in combination with eribulin in HER2-negative metastatic breast cancer: A phase IB/II study (KCSG BR18-16).

机构信息

Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.

Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University, College of Medicine, Seoul, South Korea.

出版信息

Eur J Cancer. 2023 Dec;195:113386. doi: 10.1016/j.ejca.2023.113386. Epub 2023 Oct 14.

DOI:10.1016/j.ejca.2023.113386

PMID:37890351

Abstract

AIM

We evaluated the efficacy and safety of nivolumab and eribulin combination therapy for metastatic breast cancer (BC) in Asian populations.

METHODS

In this parallel phase II study, adult patients with histologically confirmed recurrent/metastatic hormone receptor-positive/HER2-negative (HR+HER2-) or triple-negative BC (TNBC) were prospectively enroled from 10 academic hospitals in Korea (ClinicalTrials.gov Identifier: NCT04061863). They received nivolumab (360 mg) on day 1 plus eribulin (1.4 mg/m) on days 1 and 8 every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was the investigator-assessed 6-month progression-free survival (PFS) rate in each subtype. Secondary endpoints included investigator-assessed objective response rate (ORR) as per Response Evaluation Criteria in Advanced Solid Tumors version 1.1, disease control rate, overall survival, and treatment toxicity. The association between PD-L1 expression and efficacy was investigated.

RESULTS

Forty-five patients with HR+HER2- BC and 45 with TNBC were enroled. Their median age was 51 (range, 31-71) years, and 74 (82.2%) received one or two prior treatments before enrolment. Six-month PFS was 47.2% and 25.1% in the HR+HER2- and TNBC cohorts, respectively. Median PFS was 5.6 (95% confidence interval [CI]: 5.3-7.4) and 3.0 (95% CI: 2.1-5.2) months in the HR+HER2- and TNBC groups, respectively. ORRs were 53.3% (complete response [CR]: 0, partial response [PR]: 24) and 28.9% (CR: 1, PR: 12). Patients with PD-L1+ tumours (PD-L1 expression ≥1%) and PD-L1- tumours (ORR 50% versus 53.8% in HR+HER2-, 30.8% versus 29.0% in TNBC) had similar ORRs. Neutropenia was the most common grade 3/4 adverse event; the most common immune-related adverse events (AEs) were grades 1/2 hypothyroidism and pruritus. Five patients discontinued therapy because of immune-related AEs.

CONCLUSION

Nivolumab plus eribulin showed promising efficacy and tolerable safety in previously treated HER2- metastatic BC.

TRIAL REGISTRATION

NCT04061863.

摘要

目的

我们评估了纳武利尤单抗联合艾立布林治疗亚洲转移性乳腺癌（MBC）的疗效和安全性。

方法

这是一项平行的 II 期研究，来自韩国 10 家学术医院的组织学确诊的复发性/转移性激素受体阳性/HER2 阴性（HR+HER2-）或三阴性乳腺癌（TNBC）成年患者前瞻性入组（ClinicalTrials.gov 标识符：NCT04061863）。他们每 3 周接受一次纳武利尤单抗（360mg）加艾立布林（1.4mg/m），第 1 天和第 8 天，直至疾病进展或无法耐受毒性。主要终点是每个亚型研究者评估的 6 个月无进展生存期（PFS）率。次要终点包括研究者根据实体瘤反应评价标准 1.1 评估的客观缓解率（ORR）、疾病控制率、总生存期和治疗毒性。还研究了 PD-L1 表达与疗效的关系。

结果

共纳入 45 例 HR+HER2- BC 患者和 45 例 TNBC 患者。他们的中位年龄为 51 岁（范围，31-71 岁），74 例（82.2%）在入组前接受过一次或两次治疗。HR+HER2- 和 TNBC 队列的 6 个月 PFS 率分别为 47.2%和 25.1%。HR+HER2-和 TNBC 组的中位 PFS 分别为 5.6（95%置信区间[CI]：5.3-7.4）和 3.0（95% CI：2.1-5.2）个月。ORR 分别为 53.3%（完全缓解[CR]：0，部分缓解[PR]：24）和 28.9%（CR：1，PR：12）。PD-L1+肿瘤（PD-L1 表达≥1%）和 PD-L1-肿瘤（HR+HER2-中 ORR 为 50%比 53.8%，TNBC 中为 30.8%比 29.0%）的 ORR 相似。中性粒细胞减少症是最常见的 3/4 级不良事件；最常见的免疫相关不良事件（AE）是 1/2 级甲状腺功能减退和瘙痒。5 例患者因免疫相关 AE 停止治疗。