Tolaney Sara M, Kalinsky Kevin, Kaklamani Virginia G, D'Adamo David R, Aktan Gursel, Tsai Michaela L, O'Regan Ruth M, Kaufman Peter A, Wilks Sharon T, Andreopoulou Eleni, Patt Debra A, Yuan Yuan, Wang Grace, Savulsky Claudio, Xing Dongyuan, Kleynerman Ella, Karantza Vassiliki, Diab Sami
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia.
Clin Cancer Res. 2021 Jun 1;27(11):3061-3068. doi: 10.1158/1078-0432.CCR-20-4726. Epub 2021 Mar 16.
As monotherapies, eribulin (chemotherapy) and pembrolizumab (immunotherapy) have shown promise for patients with metastatic triple-negative breast cancer (mTNBC). This phase Ib/II study examined eribulin plus pembrolizumab as a potential mTNBC treatment in first-line and later-line settings.
In this open-label, single-arm, phase Ib/II study, eligible patients had mTNBC, measurable disease, and ≤2 prior systemic anticancer therapies in the metastatic setting. Patients were enrolled by number of prior systemic anticancer therapies (stratum 1: 0 vs stratum 2: 1-2) in the metastatic setting and further analyzed by tumor programmed death-ligand 1 (PD-L1) expression status. All patients received intravenous eribulin 1.4 mg/m on day 1 and day 8, plus intravenous pembrolizumab 200 mg on day 1, of 21-day cycles. The primary objectives were the safety, tolerability, and objective response rate (ORR) of this combination.
The study included 167 patients (phase Ib, = 7; phase II, = 160). The most common treatment-emergent adverse events were fatigue (66%), nausea (58%), peripheral sensory neuropathy (41%), alopecia (40%), and constipation (37%). ORRs were 25.8% [95% confidence interval (CI): 15.8-38.0] for stratum 1 ( = 66) and 21.8% (95% CI: 14.2-31.1) for stratum 2 ( = 101). Patients with PD-L1-positive tumors (combined positive score ≥1) had numerically higher ORR than those with PD-L1-negative tumors, particularly in stratum 1 [stratum 1: 34.5% (95% CI: 17.9-54.3) vs 16.1% (95% CI: 5.5-33.7); stratum 2, 24.4% (95% CI: 12.9-39.5) vs 18.2% (95% CI: 8.2-32.7)].
Eribulin plus pembrolizumab was generally well tolerated and showed promising antitumor activity in mTNBC. Efficacy outcomes appeared influenced by line of therapy and PD-L1 status.
作为单一疗法，艾日布林（化疗药物）和帕博利珠单抗（免疫疗法）已显示出对转移性三阴性乳腺癌（mTNBC）患者具有治疗前景。这项Ib/II期研究考察了艾日布林联合帕博利珠单抗作为一线和后续治疗中mTNBC的潜在治疗方案。
在这项开放标签、单臂、Ib/II期研究中，符合条件的患者患有mTNBC、具有可测量病灶，且在转移情况下既往接受过≤2种全身抗癌治疗。患者根据转移情况下既往全身抗癌治疗的次数（第1层：0次 vs 第2层：1 - 2次）进行入组，并根据肿瘤程序性死亡配体1（PD-L1）表达状态进一步分析。所有患者在21天周期的第1天和第8天接受静脉注射艾日布林1.4 mg/m²，在第1天接受静脉注射帕博利珠单抗200 mg。主要目标是该联合治疗方案的安全性、耐受性和客观缓解率（ORR）。
该研究纳入了167例患者（Ib期，n = 7；II期，n = 160）。最常见的治疗中出现的不良事件为疲劳（66%）、恶心（58%）、外周感觉神经病变（41%）、脱发（40%）和便秘（37%）。第1层（n = 66）的ORR为25.8% [95%置信区间（CI）：15.8 - 38.0]，第2层（n = 101）的ORR为21.8%（95% CI：14.2 - 31.1）。PD-L1阳性肿瘤（综合阳性评分≥1）的患者ORR在数值上高于PD-L1阴性肿瘤患者，尤其是在第1层[第1层：34.5%（95% CI：17.9 - 54.3） vs 16.1%（95% CI：5.5 - 33.7）；第2层，24.4%（95% CI：12.9 - 39.5） vs 18.2%（95% CI：8.2 - 32.7）]。
艾日布林联合帕博利珠单抗总体耐受性良好，在mTNBC中显示出有前景的抗肿瘤活性。疗效结果似乎受治疗线数和PD-L1状态影响。
