一线使用伊匹单抗和纳武单抗治疗的转移性肾细胞癌患者间歇性治疗的II期试验

Phase II Trial of Intermittent Therapy in Patients with Metastatic Renal Cell Carcinoma Treated with Front-line Ipilimumab and Nivolumab.

作者信息

Ornstein Moshe C, George Laeth, Wei Wei, Diaz-Montero C Marcela, Rayman Pat, Martin Allison, Basu Arnab, Beckermann Kathryn E, Nizam Amanda, Wee Christopher E, Gilligan Timothy D, Gupta Shilpa, Rini Brian I

机构信息

Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.

出版信息

Clin Genitourin Cancer. 2024 Dec;22(6):102181. doi: 10.1016/j.clgc.2024.102181. Epub 2024 Jul 31.

DOI:10.1016/j.clgc.2024.102181

PMID:39208489

Abstract

INTRODUCTION

The combination of ipilimumab/nivolumab is approved for patients with treatment-naïve, intermediate-, and poor-risk metastatic renal cell carcinoma (mRCC), but duration of therapy and safety/efficacy of reinduction at progression is unknown. A phase II trial of intermittent ipilimumab/nivolumab with reinduction at progression was conducted (NCT03126331).

PATIENTS AND METHODS

Patients with treatment-naïve mRCC were treated with induction ipilimumab/nivolumab followed by up to 24 weeks of maintenance nivolumab. Patients who achieved a complete response (CR) or partial response (PR) were eligible for inclusion and entered a treatment-free observation period. Patients were restaged every 12 weeks. Patients with no disease progression (PD) remained off therapy. Upon PD, patients were re-challenged with 2 doses of ipilimumab/nivolumab every 3 weeks. Study objectives were to estimate success rate of observation in patients who achieve a CR/PR, and to assess toxicity in patients undergoing reinduction. The study accrued slower than expected and was closed prior to the anticipated accrual goal of 20 patients.

RESULTS

Nine patients were included; 89% male, median age 57, 67% clear-cell histology, and 78% intermediate-risk by IMDC criteria. Response to ipilimumab/nivolumab followed by nivolumab maintenance prior to enrollment was 33% CR and 67% PR. Most (78%) patients have remained off therapy, with a median treatment-free interval (TFI) of 34.3 months (range, 8.7-41.8). Two patients had PD off therapy and received 2 cycles of reinduction ipilimumab and nivolumab. No grade 3 or greater toxicities occurred with reinduction. Both patients developed PD at their first scans after reinduction.

CONCLUSION

This prospective study demonstrates that patients with a radiographic response to ipilimumab/nivolumab can have prolonged treatment-free intervals. Further studies of de-escalation strategies are warranted.

TRIAL REGISTRATION

NCT03126331 [Date of registration 4/27/2017; https://clinicaltrials.gov/ct2/show/NCT03126331].

摘要

引言

伊匹单抗/纳武单抗联合用药已被批准用于初治、中危和低危转移性肾细胞癌（mRCC）患者，但治疗持续时间以及疾病进展时再次诱导治疗的安全性/有效性尚不清楚。开展了一项关于伊匹单抗/纳武单抗间歇性给药并在疾病进展时再次诱导治疗的II期试验（NCT03126331）。

患者与方法

初治mRCC患者先接受伊匹单抗/纳武单抗诱导治疗，随后接受长达24周的纳武单抗维持治疗。达到完全缓解（CR）或部分缓解（PR）的患者有资格入组并进入无治疗观察期。患者每12周重新分期。无疾病进展（PD）的患者继续停药。疾病进展时，患者每3周接受2剂伊匹单抗/纳武单抗再次治疗。研究目的是评估达到CR/PR的患者的观察成功率，并评估再次诱导治疗患者的毒性。该研究入组速度慢于预期，在预期入组20例患者的目标之前就提前结束了。

结果

纳入9例患者；男性占89%，中位年龄57岁，67%为透明细胞组织学类型，根据IMDC标准78%为中危。入组前接受伊匹单抗/纳武单抗治疗后再接受纳武单抗维持治疗的缓解率为33%CR和67%PR。大多数（78%）患者持续停药，中位无治疗间隔（TFI）为34.3个月（范围8.7 - 41.8个月）。2例患者在停药期间出现疾病进展，接受了2个周期的伊匹单抗和纳武单抗再次诱导治疗。再次诱导治疗未出现3级或更高级别的毒性反应。2例患者在再次诱导治疗后的首次扫描时均出现疾病进展。