在未发生疾病进展的情况下停用 durvalumab 的经治患者中的 durvalumab 活性。
Durvalumab activity in previously treated patients who stopped durvalumab without disease progression.
机构信息
Division of Medical Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Clinical Development Oncology, Oncology Research and Development, AstraZeneca, Gaithersburg, Maryland, USA.
出版信息
J Immunother Cancer. 2020 Aug;8(2). doi: 10.1136/jitc-2020-000650.
BACKGROUND
Limited data exist on potential clinical benefit with anti-programmed cell death ligand-1 (PD-L1) retreatment in patients who stop initial therapy for reasons other than disease progression or toxicity and develop disease progression while off treatment.
PATIENTS AND METHODS
NCT01693562 was a phase I/II study evaluating durvalumab monotherapy in advanced solid tumors. Patients benefiting from treatment were taken off durvalumab at 1 year per protocol and prospectively followed. At disease progression, they were eligible for durvalumab retreatment. Outcomes evaluated during retreatment included best overall response (BOR2), duration of response (DoR2), disease control rate (DCR2), and progression-free survival (PFS2).
RESULTS
Of 980 patients enrolled and treated with durvalumab 10 mg/kg every 2 weeks (Q2W) in the dose-expansion cohorts, 168 completed 1 year of initial durvalumab treatment with confirmed BOR1 of complete response in 20 (11.9%), partial response (PR) in 84 (50%), stable disease (SD) in 52 (31%), and disease progression in 12 (7.1%). All 168 patients stopped treatment and were eligible for retreatment at progression; 70 patients (41.7%) representing 14 primary tumor types were retreated and response evaluable. Confirmed BOR2 was PR in 8 patients (11.4%), SD in 42 (60.0%), disease progression in 16 (22.9%), and unevaluable in 4 (5.7%). Median DoR2 was 16.5 months. DCR2 ≥24 weeks (DCR2 24) was 47.1%. PFS2 rate at 12 months was 34.2%, and median PFS2 was 5.9 months. Median overall survival (OS2) was 23.8 months. Response rates, DCR2 24, and median DoR2 were generally greater in patients with high PD-L1 expression than those with low/negative expression. No new safety signals were observed during retreatment.
CONCLUSION
Retreatment restored antitumor activity, resulting in high rates of durable disease control with an acceptable safety profile. This evidence supports retreatment of patients who stop anti-PD-L1 therapy for reasons other than progression or toxicity, and supports further investigation.
背景
对于因非疾病进展或毒性而停止初始治疗且在停药期间发生疾病进展的患者，抗程序性细胞死亡配体 1（PD-L1）的再治疗可能具有潜在的临床获益，但相关数据有限。
方法
NCT01693562 是一项评估单药 durvalumab 治疗晚期实体瘤的 I/II 期研究。根据方案，接受治疗的患者在 1 年后停用 durvalumab，并进行前瞻性随访。疾病进展时，他们有资格接受 durvalumab 再治疗。再治疗期间评估的结局包括最佳总缓解（BOR2）、缓解持续时间（DoR2）、疾病控制率（DCR2）和无进展生存期（PFS2）。
结果
在剂量扩展队列中，980 例接受 durvalumab 10mg/kg、每 2 周（Q2W）治疗的患者中，168 例完成了 1 年的初始 durvalumab 治疗，确认的 BOR1 为完全缓解（CR）20 例（11.9%），部分缓解（PR）84 例（50%），疾病稳定（SD）52 例（31%），疾病进展 12 例（7.1%）。所有 168 例患者停止治疗并在进展时符合再治疗条件；70 例（41.7%）代表 14 种主要肿瘤类型的患者接受了再治疗并可评估疗效。确认的 BOR2 为 PR 8 例（11.4%），SD 42 例（60.0%），疾病进展 16 例（22.9%），不可评估 4 例（5.7%）。中位 DoR2 为 16.5 个月。DCR2≥24 周（DCR224）为 47.1%。12 个月时的 PFS2 率为 34.2%，中位 PFS2 为 5.9 个月。中位总生存期（OS2）为 23.8 个月。高 PD-L1 表达患者的缓解率、DCR224 和中位 DoR2 一般高于低/阴性表达患者。在再治疗期间未观察到新的安全性信号。
结论
再治疗恢复了抗肿瘤活性，产生了高比例的持久疾病控制，安全性可接受。该证据支持对因非疾病进展或毒性而停止抗 PD-L1 治疗的患者进行再治疗，并支持进一步研究。
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