Office of Oncologic Diseases, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Oncologist. 2021 Apr;26(4):318-324. doi: 10.1002/onco.13646. Epub 2021 Jan 11.
On June 10, 2020, the U.S. Food and Drug Administration (FDA) approved nivolumab (OPDIVO; Bristol Myers Squibb, New York, NY) for the treatment of patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy. Approval was based on the results of a single, randomized, active-control study (ATTRACTION-3) that randomized patients to receive nivolumab or investigator's choice of taxane chemotherapy (docetaxel or paclitaxel). The study demonstrated a significant improvement in overall survival (OS; hazard ratio = 0.77; 95% confidence interval: 0.62-0.96; p = .0189) with an estimated median OS of 10.9 months in the nivolumab arm compared with 8.4 months in the chemotherapy arm. Overall, fewer patients in the nivolumab arm experienced treatment-emergent adverse events (TEAEs) of any grade, grade 3-4 TEAEs, and serious adverse events compared with the control arm. The safety profile of nivolumab in patients with ESCC was generally similar to the known safety profile of nivolumab in other cancer types with the following exception: esophageal fistula was identified as a new, clinically significant risk in patients with ESCC treated with nivolumab. Additionally, the incidence of pneumonitis was higher in the ESCC population than in patients with other cancer types who are treated with nivolumab. This article summarizes the FDA review of the data supporting the approval of nivolumab for the treatment of ESCC. IMPLICATIONS FOR PRACTICE: The approval of nivolumab for the treatment of adult patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy was based on an overall survival (OS) benefit from a randomized, open-label, active-controlled study called ATTRACTION-3. Prior to this study, no drug or combination regimen had demonstrated an OS benefit in a randomized study for patients with ESCC after prior fluoropyrimidine- and platinum-based chemotherapy.
2020 年 6 月 10 日，美国食品和药物管理局（FDA）批准nivolumab（OPDIVO；百时美施贵宝，纽约，NY）用于先前接受氟嘧啶和铂类化疗后不可切除的晚期、复发性或转移性食管鳞状细胞癌（ESCC）患者的治疗。批准基于一项单臂、随机、阳性对照研究（ATTRACTION-3）的结果，该研究将患者随机分配接受 nivolumab 或研究者选择的紫杉烷化疗（多西他赛或紫杉醇）。研究表明，与化疗组相比，nivolumab 组的总生存期（OS）显著改善（风险比=0.77；95%置信区间：0.62-0.96；p=0.0189），nivolumab 组的估计中位 OS 为 10.9 个月，而化疗组为 8.4 个月。总体而言，与对照组相比，nivolumab 组出现任何级别、3-4 级治疗相关不良事件（TEAE）和严重不良事件的患者更少。在 ESCC 患者中，nivolumab 的安全性概况与其他癌症类型中已知的 nivolumab 安全性概况大致相似，以下为例外情况：与接受 nivolumab 治疗的 ESCC 患者相比，食管瘘被确定为一种新的、有临床意义的风险。此外，在接受 nivolumab 治疗的 ESCC 患者中，肺炎的发生率高于接受 nivolumab 治疗的其他癌症类型患者。本文总结了 FDA 对支持 nivolumab 治疗 ESCC 的数据的审查。对实践的影响：在先前接受氟嘧啶和铂类化疗后不可切除的晚期、复发性或转移性食管鳞状细胞癌（ESCC）患者中，nivolumab 的批准是基于一项名为 ATTRACTION-3 的随机、开放标签、阳性对照研究的总生存期（OS）获益。在此研究之前，没有药物或联合方案在先前接受氟嘧啶和铂类化疗后随机研究中显示出对 ESCC 患者的 OS 获益。
