法米替尼联合卡瑞利珠单抗和白蛋白紫杉醇治疗晚期免疫调节型三阴性乳腺癌（FUTURE-C-Plus）：一项开放标签、单臂、Ⅱ期临床试验。
Famitinib with Camrelizumab and Nab-Paclitaxel for Advanced Immunomodulatory Triple-Negative Breast Cancer (FUTURE-C-Plus): An Open-Label, Single-Arm, Phase II Trial.
机构信息
Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College of Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China.
出版信息
Clin Cancer Res. 2022 Jul 1;28(13):2807-2817. doi: 10.1158/1078-0432.CCR-21-4313.
PURPOSE
Camrelizumab, an mAb against programmed cell death protein 1 (PD-1), plus nab-paclitaxel exhibited promising antitumor activity in refractory metastatic immunomodulatory triple-negative breast cancer (TNBC). Famitinib is a tyrosine kinase inhibitor targeting VEGFR2, PDGFR, and c-kit. We aimed to assess the efficacy and safety of a novel combination of famitinib, camrelizumab, and nab-paclitaxel in advanced immunomodulatory TNBC.
PATIENTS AND METHODS
This open-label, single-arm, phase II study enrolled patients with previously untreated, advanced, immunomodulatory TNBC (CD8 IHC staining ≥10%). Eligible patients received 20 mg of oral famitinib on days 1 to 28, 200 mg of i.v. camrelizumab on days 1 and 15, and i.v. nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 in 4-week cycles. The primary endpoint was objective response rate (ORR), as assessed by investigators per RECIST v1.1. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and exploratory biomarkers.
RESULTS
Forty-eight patients were enrolled and treated. Median follow-up was 17.0 months (range, 8.7-24.3). Confirmed ORR was 81.3% [95% confidence interval (CI), 70.2-92.3], with five complete and 34 partial responses. Median PFS was 13.6 months (95% CI, 8.4-18.8), and median DOR was 14.9 months [95% CI, not estimable (NE)-NE]. Median OS was not reached. No treatment-related deaths were reported. Among 30 patients with IHC, 13 (43.3%) were programmed death-ligand 1 (PD-L1)-negative, and PD-L1 was associated with favorable response. PKD1 and KAT6A somatic mutations were associated with therapy response.
CONCLUSIONS
The triplet regimen was efficacious and well tolerated in previously untreated, advanced, immunomodulatory TNBC. The randomized controlled FUTURE-SUPER trial is under way to validate our findings. See related commentary by Salgado and Loi, p. 2728.
目的
卡瑞利珠单抗（一种针对程序性死亡蛋白 1（PD-1）的单克隆抗体）联合nab-紫杉醇在难治性转移性免疫调节性三阴性乳腺癌（TNBC）中显示出有前景的抗肿瘤活性。法米替尼是一种针对 VEGFR2、PDGFR 和 c-kit 的酪氨酸激酶抑制剂。我们旨在评估新型联合疗法（法米替尼、卡瑞利珠单抗和 nab-紫杉醇）在晚期免疫调节性 TNBC 中的疗效和安全性。
患者和方法
这是一项开放标签、单臂、Ⅱ期研究，纳入了未经治疗的晚期免疫调节性 TNBC 患者（CD8 IHC 染色≥10%）。符合条件的患者接受 28 天周期内的 20mg 口服法米替尼（第 1-28 天）、200mg 静脉注射卡瑞利珠单抗（第 1 天和第 15 天）和 100mg/m2 静脉注射 nab-紫杉醇（第 1 天、第 8 天和第 15 天）。主要终点为研究者根据 RECIST v1.1 评估的客观缓解率（ORR）。次要终点包括无进展生存期（PFS）、总生存期（OS）、缓解持续时间（DOR）、安全性和探索性生物标志物。
结果
共纳入 48 例患者进行治疗。中位随访时间为 17.0 个月（范围：8.7-24.3）。确认的 ORR 为 81.3%[95%置信区间（CI）：70.2-92.3]，包括 5 例完全缓解和 34 例部分缓解。中位 PFS 为 13.6 个月（95%CI：8.4-18.8），中位 DOR 为 14.9 个月[95%CI：无法估计（NE）-NE]。中位 OS 未达到。未报告与治疗相关的死亡。在 30 例有 IHC 数据的患者中，有 13 例（43.3%）PD-L1 阴性，PD-L1 与良好的反应相关。PKD1 和 KAT6A 体细胞突变与治疗反应相关。
结论
在未经治疗的晚期免疫调节性 TNBC 中，三联疗法具有疗效且耐受性良好。正在进行的随机对照 FUTURE-SUPER 试验旨在验证我们的研究结果。详见 Salgado 和 Loi 的相关评论，第 2728 页。
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