立体定向体部放疗联合非一线 PD-1 抑制剂和靶向药物治疗转移性肾细胞癌。

Stereotactic body radiotherapy in combination with non-frontline PD-1 inhibitors and targeted agents in metastatic renal cell carcinoma.

机构信息

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.

Department of Urology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.

出版信息

Radiat Oncol. 2021 Nov 2;16(1):211. doi: 10.1186/s13014-021-01937-9.

DOI:10.1186/s13014-021-01937-9

PMID:34727963

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8561986/

Abstract

BACKGROUND

Radiotherapy may work synergistically with immunotherapy and targeted agents. We aimed to assess the safety and outcomes of stereotactic body radiotherapy (SBRT) plus non-first-line programmed death-1 (PD-1) inhibitors and targeted agents (TA) in metastatic renal cell carcinoma (mRCC).

METHODS

We retrospectively reviewed 74 patients treated with non-first-line PD-1 inhibitors plus TA in non-first-line setting. Survival outcomes were calculated from the anti-PD-1 treatment using the Kaplan-Meier method. Univariate and multivariate analyses were performed by Cox proportional hazards models.

RESULTS

Thirty-two (43.2%) patients received anti-PD-1/TA therapy alone (anti-PD-1/TA alone group), and 42 (56.8%) received SBRT in addition (anti-PD-1/TA + SBRT group). The median duration of first-line therapy was 8.6 months. Patients in the anti-PD-1/TA + SBRT group had significantly longer overall survival (OS) (38.5 vs 15.4 months; P = 0.022). On multivariate analysis, oligometastasis, ECOG performance status 0-1, anti-PD-1/TA + SBRT, and duration of first-line therapy ≥ 8.6 months were predictors for OS. The addition of SBRT was associated with improved OS in patients with clear-cell type (HR 0.19; 95% CI 0.07-0.55; P = 0.002) and duration of first-line therapy ≥ 8.6 months (HR 0.22; 95% CI 0.06-0.88; P = 0.032). Grade ≥ 3 toxicities occurred in 23 patients (54.8%) in the anti-PD-1/TA + SBRT group, and in 21 patients (65.6%) in the anti-PD-1/TA alone group.

CONCLUSIONS

Incorporating SBRT into anti-PD-1/TA therapy is safe and tolerable. Further investigation is needed, particularly in patients with clear-cell histology and a longer duration of response to first-line antiangiogenic therapy.

摘要

背景

放疗可能与免疫治疗和靶向药物协同作用。我们旨在评估立体定向体部放疗（SBRT）联合非一线程序性死亡受体-1（PD-1）抑制剂和靶向药物（TA）在转移性肾细胞癌（mRCC）中的安全性和疗效。

方法

我们回顾性分析了 74 例接受非一线 PD-1 抑制剂联合 TA 治疗的患者。采用 Kaplan-Meier 法从抗 PD-1 治疗开始计算生存结局。采用 Cox 比例风险模型进行单因素和多因素分析。

结果

32 例（43.2%）患者接受抗 PD-1/TA 单药治疗（抗 PD-1/TA 单药组），42 例（56.8%）患者接受 SBRT 治疗（抗 PD-1/TA+SBRT 组）。一线治疗的中位持续时间为 8.6 个月。抗 PD-1/TA+SBRT 组的总生存期（OS）明显延长（38.5 个月比 15.4 个月；P=0.022）。多因素分析显示，寡转移、ECOG 表现状态 0-1、抗 PD-1/TA+SBRT 和一线治疗持续时间≥8.6 个月是 OS 的预测因素。在接受 SBRT 治疗的患者中，透明细胞型（HR 0.19；95%CI 0.07-0.55；P=0.002）和一线治疗持续时间≥8.6 个月（HR 0.22；95%CI 0.06-0.88；P=0.032）的 OS 得到改善。抗 PD-1/TA+SBRT 组 23 例（54.8%）和抗 PD-1/TA 单药组 21 例（65.6%）患者发生≥3 级毒性。