Shah Mirat, Osgood Christy L, Amatya Anup K, Fiero Mallorie H, Pierce William F, Nair Abhilasha, Herz Jonathan, Robertson Kim J, Mixter Bronwyn D, Tang Shenghui, Pazdur Richard, Beaver Julia A, Amiri-Kordestani Laleh
Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, Maryland.
Clin Cancer Res. 2022 Dec 15;28(24):5249-5253. doi: 10.1158/1078-0432.CCR-22-1110.
On July 26, 2021, the FDA granted approval to pembrolizumab in combination with chemotherapy for neoadjuvant treatment and then continued as a single agent for adjuvant treatment following surgery for patients with high-risk, early-stage triple-negative breast cancer. Approval was based on results from KEYNOTE-522, an ongoing randomized (2:1) trial evaluating pembrolizumab or placebo in combination with chemotherapy for neoadjuvant treatment and then as a single agent for adjuvant treatment. The co-primary endpoints were pathological complete response (pCR) rate and event-free survival (EFS). The trial demonstrated an improvement in pCR and EFS in the pembrolizumab arm compared with the control arm. The number of patients who experienced an EFS event was 123 (16%) and 93 (24%), respectively [HR: 0.63, 95% confidence interval (CI), 0.48-0.82, P = 0.00031]. Patients on the pembrolizumab arm experienced EFS benefit regardless of tumor PD-L1 status. The absolute pCR rate improvement with the addition of pembrolizumab was 7.5% (95% CI, 1.6-13.4). Among patients receiving pembrolizumab, 44% experienced an immune-related adverse reaction. This article summarizes FDA's review of pembrolizumab and the data supporting the favorable benefit-risk assessment.
2021年7月26日，美国食品药品监督管理局（FDA）批准帕博利珠单抗联合化疗用于新辅助治疗，术后继续作为单药用于高危早期三阴性乳腺癌患者的辅助治疗。批准基于KEYNOTE-522试验结果，这是一项正在进行的随机（2:1）试验，评估帕博利珠单抗或安慰剂联合化疗用于新辅助治疗，然后作为单药用于辅助治疗。共同主要终点为病理完全缓解（pCR）率和无事件生存期（EFS）。试验表明，与对照组相比，帕博利珠单抗组的pCR和EFS有所改善。发生EFS事件的患者数量分别为123例（16%）和93例（24%）[风险比（HR）：0.63，95%置信区间（CI），0.48 - 0.82，P = 0.00031]。帕博利珠单抗组的患者无论肿瘤程序性死亡受体配体1（PD-L1）状态如何均有EFS获益。添加帕博利珠单抗后pCR率的绝对改善为7.5%（95% CI，1.6 - 13.4）。接受帕博利珠单抗治疗的患者中，44%出现免疫相关不良反应。本文总结了FDA对帕博利珠单抗的审评以及支持有利获益风险评估的数据。
