Kidney Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, United States; Gustave Roussy Cancer Campus, University of Paris Sud, Department of Cancer Medicine, Villejuif, France.
Kidney Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, United States.
Eur J Cancer. 2015 Nov;51(17):2580-6. doi: 10.1016/j.ejca.2015.08.017. Epub 2015 Sep 4.
Monoclonal antibodies that target the programmed death-1 (PD-1)/programmed death-ligand 1(PD-L1) pathway have shown antitumour activity in metastatic renal cell carcinoma (mRCC) and are currently being developed in first-line (in combination) and in previously treated patients. The efficacy targeted therapy (TT) after PD-1/PD-L1 blockade is still unknown.
Medical records of mRCC patients treated with investigational PD-1 or PD-L1 inhibitors at 4 academic institutions were reviewed. Patients who received subsequent treatment with TT were selected to collect outcome measures of subsequent TT.
Of 99 patients who received PD-1/PD-L1 blockade as part of clinical trials, 56 patients have received subsequent therapy: 44 patients received vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) inhibitors and 12 received mammalian target of rapamycin (mTOR) inhibitors as first subsequent TT. Median follow up, from the start of subsequent TT was 16.1 months (range: 0.2, 30.6 months). TT post PD-1/PD-L1 blockade was administered as second-line, third-line or beyond third-line in 9 (16%), 24 (43%) and 23 patients (41%) respectively. Median time to treatment failure on subsequent TT was 6.6 months (range: 0.2+, 23.0). 1-year and 2 year overall survival from the initiation of subsequent TT was 58% (95% confidence interval (CI): 41-72%) and 36% (95% CI: 18-54%), respectively.
Both VEGF/VEGFR and mTOR inhibitors demonstrate antitumour activity following PD-1/PD-L1 blockade.
针对程序性死亡-1（PD-1）/程序性死亡配体 1（PD-L1）通路的单克隆抗体在转移性肾细胞癌（mRCC）中显示出抗肿瘤活性，目前正在一线（联合）和既往治疗患者中进行开发。PD-1/PD-L1 阻断后的靶向治疗（TT）的疗效仍不清楚。
回顾了 4 家学术机构接受研究性 PD-1 或 PD-L1 抑制剂治疗的 mRCC 患者的病历。选择接受 TT 后续治疗的患者收集后续 TT 的结果指标。
在接受 PD-1/PD-L1 阻断作为临床试验一部分的 99 名患者中，56 名患者接受了后续治疗：44 名患者接受了血管内皮生长因子（VEGF）/血管内皮生长因子受体（VEGFR）抑制剂，12 名患者接受了哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂作为首次后续 TT。自后续 TT 开始的中位随访时间为 16.1 个月（范围：0.2-30.6 个月）。TT 后 PD-1/PD-L1 阻断的给药分别为二线、三线或三线以上，分别为 9（16%）、24（43%）和 23 名患者（41%）。后续 TT 的治疗失败中位时间为 6.6 个月（范围：0.2+，23.0）。从后续 TT 开始的 1 年和 2 年总生存率分别为 58%（95%置信区间（CI）：41-72%）和 36%（95% CI：18-54%）。
VEGF/VEGFR 和 mTOR 抑制剂在 PD-1/PD-L1 阻断后均显示出抗肿瘤活性。
