Garon Edward B, Visseren-Grul Carla, Rizzo Maria Teresa, Puri Tarun, Chenji Suresh, Reck Martin
David Geffen School of Medicine, University of California, Los Angeles/Translational Research in Oncology-United States Network, Los Angeles, CA, United States.
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, United States.
Front Oncol. 2023 Sep 4;13:1247879. doi: 10.3389/fonc.2023.1247879. eCollection 2023.
In the REVEL trial, ramucirumab plus docetaxel demonstrated significant improvements in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) compared with placebo plus docetaxel for treatment of metastatic non-small cell lung cancer (NSCLC) that progressed during or after platinum-based chemotherapy. Since the approval of ramucirumab plus docetaxel, immune checkpoint inhibitors (ICIs), either as single agents or in combination with chemotherapy, have become the standard of care for first-line treatment of patients with advanced NSCLC. However, efficacy and safety data for ramucirumab plus docetaxel after prior ICI treatment from randomized controlled clinical studies are lacking.
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature review was performed. Electronic databases and select international oncology conference proceedings were searched. Studies published between 01 January 2014 and 01 July 2022, which evaluated 2 efficacy outcomes (and included at least 1 time-to-event endpoint) or safety outcomes of ramucirumab plus docetaxel in NSCLC that progressed after prior ICI treatment, were identified. Twelve studies were included in the analysis. Two treatment groups were selected: ramucirumab plus docetaxel after prior ICI ± chemotherapy (RAM + DTX ICI pre-treated) and ramucirumab plus docetaxel after prior chemotherapy only (RAM + DTX ICI naïve). OS, PFS, ORR, disease control rate (DCR), and safety data were extracted and descriptively summarized across both treatment groups.
The pooled weighted median PFS and median OS were 5.7 months (95% confidence interval [CI]: 3.9-6.8) and 11.2 months (95% CI: 7.5-17.5), respectively, in the RAM + DTX ICI pre-treated group and 3.8 months (95% CI: 2.3-4.1) and 13.5 months (95% CI: 8-24.0), respectively, in the RAM + DTX ICI naïve group. The ORR and DCR ranged from 20.9% to 60.0% and from 62.4% to 90.0%, respectively, in the RAM + DTX ICI pre-treated group and from 17.7% to 20.0% and from 57.1% to 75.0%, respectively, in the RAM + DTX ICI naïve group. The safety profile across studies was consistent between both treatment groups, and no new safety signals were reported.
Cumulatively, these results support the combination of ramucirumab plus docetaxel as an effective and safe subsequent therapy for the treatment of patients with metastatic NSCLC with disease progression irrespective of previous ICI treatment.
在REVEL试验中,与安慰剂联合多西他赛相比,雷莫西尤单抗联合多西他赛在治疗铂类化疗期间或之后进展的转移性非小细胞肺癌(NSCLC)时,总生存期(OS)、无进展生存期(PFS)和总缓解率(ORR)均有显著改善。自雷莫西尤单抗联合多西他赛获批以来,免疫检查点抑制剂(ICI)无论是作为单药还是与化疗联合,都已成为晚期NSCLC患者一线治疗的标准方案。然而,缺乏来自随机对照临床研究的关于雷莫西尤单抗联合多西他赛在先前ICI治疗后的疗效和安全性数据。
按照系统评价和Meta分析的首选报告项目(PRISMA)指南进行系统文献综述。检索了电子数据库和精选的国际肿瘤学会议论文集。纳入了2014年1月1日至2022年7月1日期间发表的研究,这些研究评估了雷莫西尤单抗联合多西他赛在先前ICI治疗后进展的NSCLC中的2项疗效指标(并至少包括1个事件发生时间终点)或安全性指标。分析纳入了12项研究。选择了两个治疗组:先前接受ICI±化疗后使用雷莫西尤单抗联合多西他赛(雷莫西尤单抗联合多西他赛经ICI预处理)和仅先前接受化疗后使用雷莫西尤单抗联合多西他赛(雷莫西尤单抗联合多西他赛未接受ICI治疗)。提取了两个治疗组的OS、PFS、ORR、疾病控制率(DCR)和安全性数据,并进行描述性汇总。
在雷莫西尤单抗联合多西他赛经ICI预处理组中,汇总加权中位PFS和中位OS分别为5.7个月(95%置信区间[CI]:3.9 - 6.8)和11.2个月(95%CI:7.5 - 17.5),在雷莫西尤单抗联合多西他赛未接受ICI治疗组中分别为3.8个月(95%CI:2.3 - 4.1)和13.5个月(95%CI:8 - 24.0)。在雷莫西尤单抗联合多西他赛经ICI预处理组中,ORR和DCR分别为20.9%至60.0%和62.4%至90.0%,在雷莫西尤单抗联合多西他赛未接受ICI治疗组中分别为17.7%至20.0%和57.1%至75.0%。两个治疗组的研究安全性概况一致,未报告新的安全信号。
总体而言,这些结果支持雷莫西尤单抗联合多西他赛作为一种有效且安全的后续治疗方案,用于治疗疾病进展的转移性NSCLC患者,无论之前是否接受过ICI治疗。