Levy Antonin, Massard Christophe, Soria Jean-Charles, Deutsch Eric
Department of Radiation Oncology, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France; DITEP, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France; INSERM U1030, Molecular Radiotherapy, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France; University Paris Sud, Université Paris-Saclay, F-94270, Le Kremlin-Bicêtre, France.
DITEP, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France.
Eur J Cancer. 2016 Nov;68:156-162. doi: 10.1016/j.ejca.2016.09.013. Epub 2016 Oct 17.
To assess preliminary safety and efficacy results of the anti-programmed cell death ligand-1 (anti-PD-L1) durvalumab in combination with radiotherapy (RT) in an expansion cohort of patients included in a phase 1/2 trial at our institution.
Data from patients who received concurrent palliative RT with durvalumab (10 mg/kg every 2 weeks via intravenous infusion) were analysed in terms of safety (CTCAE v4.0) and efficacy (RECIST v1.1 and tumour growth rate [TGR]).
Between 02/2014 and 04/2016, 10 patients received palliative local irradiation of 15 isolated lesions. Most patients (90%) had received one or more prior lines of systemic therapy for advanced disease. The median duration of exposure to durvalumab was 5.2 months with a median delivery of 11 cycles (range, 4-38 cycles). RT (conformal 3D RT, 79% and intracranial stereotactic RT, 21%) was delivered at a median biologically-effective dose of 28 Gy (range, 6-92), in a median number of five fractions (range, 1-10) and over a median duration of 6 d (range, 1-14). Five patients (50%) reported an irradiation-related adverse event (AE) grade (G) 1 or 2 and one patient had two G2 AEs. The most frequently reported AE (3/6) was G2 mucositis. There was no G3 or more RT-related AEs. All AEs were transient, lasted less than one week, and were manageable by standard guidelines. There was no unexpected AE. On 10/15 in-field (IF) evaluable lesions, the objective response (OR) rate was 60% (complete response, 2/10 and partial response, 4/10) and 4/10 stable disease (SD). All evaluated IF lesions had a TGR decrease resulting in a significant decrease in the TGR between the two periods (before versus after RT; p < 0.01). Outfields disease evaluation retrieved 10/14 SD and 4/14 progressive disease (PD). There was no out-field OR, no abscopal effect and no out-field difference between the two periods according to TGR (p = 0.09).
In this small data set of patients, concurrent palliative RT with the anti-PD-L1 durvalumab was well tolerated. ClinicalTrials.gov number: NCT01693562; EudraCT number: 2012-002206-52.
在我们机构开展的一项1/2期试验的扩展队列中，评估抗程序性细胞死亡配体1（抗PD-L1）度伐利尤单抗联合放射治疗（RT）的初步安全性和疗效结果。
分析接受度伐利尤单抗同步姑息性放疗（每2周静脉输注10mg/kg）患者的数据，评估安全性（采用CTCAE v4.0标准）和疗效（采用RECIST v1.1标准及肿瘤生长率[TGR]）。
2014年2月至2016年4月期间，10例患者接受了15个孤立病灶的姑息性局部照射。大多数患者（90%）曾接受过一种或多种晚期疾病的一线全身治疗。度伐利尤单抗的中位暴露时间为5.2个月，中位给药周期为11个周期（范围4 - 38个周期）。放疗（适形3D放疗，79%；颅内立体定向放疗，21%）的中位生物等效剂量为28Gy（范围6 - 92），中位分割次数为5次（范围1 - 10），中位疗程为6天（范围1 - 14）。5例患者（50%）报告了1级或2级放疗相关不良事件（AE），1例患者出现2次2级AE。最常报告的AE（3/6）为2级粘膜炎。未出现3级或更高级别的放疗相关AE。所有AE均为短暂性，持续时间少于1周，可按照标准指南处理。未出现意外AE。在15个野内（IF）可评估病灶中的10个中，客观缓解（OR）率为60%（完全缓解，2/10；部分缓解，4/10），4/10为疾病稳定（SD）。所有评估的IF病灶的TGR均下降，导致两个时期（放疗前与放疗后）之间的TGR显著降低（p < 0.01）。野外疾病评估显示10/14为SD，4/14为疾病进展（PD）。未出现野外OR，未出现远隔效应，两个时期之间野外TGR无差异（p = 0.09）。
在这个小样本患者数据集中，抗PD-L1度伐利尤单抗同步姑息性放疗耐受性良好。ClinicalTrials.gov编号：NCT01693562；EudraCT编号：2012 - 002206 - 52。
