Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study.
Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study.
复制标题
DOI：
10.1016/s1470-2045(21)00241-2
复制
发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Motzer RJ
中科院分区：
文献类型：
--
作者：
Lee CH;Shah AY;Rasco D;Rao A;Taylor MH;Di Simone C;Hsieh JJ;Pinto A;Shaffer DR;Girones Sarrio R;Cohn AL;Vogelzang NJ;Bilen MA;Gunnestad Ribe S;Goksel M;Tennøe ØK;Richards D;Sweis RF;Courtright J;Heinrich D;Jain S;Wu J;Schmidt EV;Perini RF;Kubiak P;Okpara CE;Smith AD;Motzer RJ
尽管转移性肾细胞癌（mRCC）的一线治疗取得了进展，但需要有效的选择来解决免疫检查点抑制剂（ICIs）治疗期间或之后的疾病进展。因此，我们的目的是评估lenvatinib + pembrolizumab在这些患者中的应用。我们报告了一项开放标签1b/2期mRCC队列研究的结果，该研究在至少18岁的选定实体瘤患者中使用lenvatinib + pembrolizumab， ECOG PS为0-1。每日口服lenvatinib 20mg，同时静脉注射pembrolizumab 200mg，每三周一次。对接受研究药物治疗的透明细胞mRCC患者的疗效进行分析，按既往治疗分组：treatment-naïve、既往治疗ICI-naïve和ci预处理患者。对所有患者进行安全性分析。主要终点是研究者根据实体瘤免疫相关反应评价标准（irRECIST）评估的第24周客观缓解率（ORRwk24）。肿瘤评估每6周进行一次，直到第24周，然后每9周进行一次。该试验已在ClinicalTrials.gov注册（NCT02501096）；最后的分析报告在这里。该研究于2015年7月21日至2019年10月16日招募了145例患者（疗效分析，n=143；安全性分析，n=145）；中位随访19.8个月（四分位数间距：14.3 ~ 28.4）。irRECIST的ORRwk24在treatment-naïve患者（16/22）中为72.7% (95% CI为49.8 - 83.3)，在先前治疗过的ICI-naïve患者（7/ 17）中为41.2% (95% CI为18.4 - 67.1)，在CI预处理患者（58/104）中为55.8% （95% CI为45.7 - 65.5）。最常见的3级治疗相关不良事件（AE）是高血压（treatment-naïve: 23%, 5/22；先前治疗ICI-naïve: 18%， 3/17； ci -预处理：21%，22/104）。36例发生治疗相关严重不良事件；其中3例发生治疗相关死亡（胃肠道出血、猝死和肺炎）。Lenvatinib + pembrolizumab显示出令人鼓舞的抗肿瘤活性和可管理的安全性，可能是ici后mRCC治疗的选择。卫材公司。默克夏普公司
Despite advances in the first-line treatment of metastatic renal cell carcinoma (mRCC), effective options are needed to address disease progression during or following treatment with immune checkpoint inhibitors (ICIs). Thus, we aimed to evaluate lenvatinib plus pembrolizumab in these patients. We report results of the mRCC cohort from an open-label phase 1b/2 study of lenvatinib plus pembrolizumab in patients at least 18 years old with selected solid tumors and an ECOG PS of 0–1. Oral lenvatinib 20 mg was given daily along with intravenous pembrolizumab 200 mg once every three weeks. Efficacy was analyzed in patients with clear cell mRCC receiving study drug by prior therapy grouping: treatment-naïve, previously treated ICI-naïve, and ICI-pretreated patients. Safety was analyzed in all patients. The primary endpoint was objective response rate at week 24 (ORRwk24) per immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) by investigator assessment. Tumor assessments occurred every six weeks until week 24, then every nine weeks. This trial is registered with ClinicalTrials.gov(NCT02501096); the final analysis is reported here. The study enrolled 145 patients (efficacy analysis, n=143; safety analysis, n=145) from July 21, 2015-October 16, 2019; median follow-up was 19·8 months (interquartile range: 14·3–28·4). The ORRwk24 by irRECIST was 72·7% (95% CI 49·8–89·3) for treatment-naïve patients (16/22), 41·2% (95% CI 18·4–67·1) for previously treated ICI-naïve patients (7/ 17), and 55·8% (95% CI 45·7–65·5) for ICI-pretreated patients (58/104). The most common grade 3 treatment-related adverse event (AE) was hypertension (treatment-naïve: 23%, 5/22; previously treated ICI-naïve: 18%, 3/17; ICI-pretreated: 21%, 22/104). Treatment-related serious AEs occurred in 36 patients; three had treatment-related deaths (gastrointestinal hemorrhage, sudden death, and pneumonia). Lenvatinib plus pembrolizumab showed encouraging antitumor activity and a manageable safety profile and may be an option for post-ICI treatment of mRCC. Eisai Inc.; Merck Sharp & Dohme Corp.