FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond.
FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond.
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DOI：
10.1634/theoncologist.2017-0078
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发表时间：
2017-11
期刊：
影响因子：
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通讯作者：
Pazdur R
中科院分区：
文献类型：
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作者：
Pai-Scherf L;Blumenthal GM;Li H;Subramaniam S;Mishra-Kalyani PS;He K;Zhao H;Yu J;Paciga M;Goldberg KB;McKee AE;Keegan P;Pazdur R
本FDA批准摘要提供了关于批准pembrolizumab用于治疗转移性非小细胞肺癌患者的更新，这些患者的肿瘤表达PD-L1，由FDA批准的检测确定。提供了KEYNOTE-010和KEYNOTE-024试验的结果。2016年10月24日，美国食品和药物管理局（FDA）批准派姆单抗（Keytruda; Merck & Co.，股份有限公司、https://www.merck.com）用于治疗转移性非小细胞肺癌（mNSCLC）患者，其肿瘤表达程序性死亡配体1（PD-L1），如FDA批准的测试所确定，如下：（a）肿瘤具有高PD-L1表达的mNSCLC患者的一线治疗（肿瘤比例评分[TPS] ≥50%），无表皮生长因子受体（EGFR）或间变性淋巴瘤激酶（ALK）肿瘤基因组畸变，和（B）治疗肿瘤表达PD-L1（TPS ≥1%）、在含铂化疗期间或之后疾病进展的mNSCLC患者。EGFR或ALK基因组肿瘤畸变患者在接受帕博利珠单抗治疗前，应在接受FDA批准的针对这些畸变的治疗后发生疾病进展。批准是基于两项随机、开放标签、活性对照试验，证明与化疗相比，随机接受pembrolizumab的患者的无进展生存期（PFS）和总生存期（OS）在统计学上显著改善。在KEYNOTE-024中，接受帕博利珠单抗治疗的既往未经治疗的mNSCLC患者（200 mg静脉注射[IV]，每3周一次）的OS改善具有统计学意义（风险比[HR] 0.60; 95%置信区间[CI]：0.41-0.89; p = .005），PFS显著改善（HR 0.50; 95% CI：0.37-0.68; p < .001）。在KEYNOTE-010中，在含铂化疗期间或之后发生疾病进展的患者接受帕博利珠单抗IV 2 mg/kg、10 mg/kg或多西他赛75 mg/m2每3周一次。OS的HR和p值为0.71（95% CI：0.58-0.88），pembrolizumab 2 mg/kg与化疗相比p <0.001，OS的HR和p值为0.61（95% CI：0.49-0.75），pembrolizumab 10 mg/kg与化疗相比p <0.001。这是美国食品和药物管理局首次批准检查点抑制剂用于肺癌的一线治疗。此次批准扩大了pembrolizumab在肺癌二线治疗中的适应症，以包括所有表达程序性死亡配体1的非小细胞肺癌患者。
This FDA approval summary provides an update on approval of pembrolizumab for treatment of patients with metastatic non‐small cell lung cancer whose tumors express PD‐L1 as determined by an FDA‐approved test. The results of KEYNOTE‐010 and KEYNOTE‐024 trials are presented. On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co., Inc., https://www.merck.com) for treatment of patients with metastatic non‐small cell lung cancer (mNSCLC) whose tumors express programmed death‐ligand 1 (PD‐L1) as determined by an FDA‐approved test, as follows: (a) first‐line treatment of patients with mNSCLC whose tumors have high PD‐L1 expression (tumor proportion score [TPS] ≥50%), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, and (b) treatment of patients with mNSCLC whose tumors express PD‐L1 (TPS ≥1%), with disease progression on or after platinum‐containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA‐approved therapy for these aberrations prior to receiving pembrolizumab. Approval was based on two randomized, open‐label, active‐controlled trials demonstrating statistically significant improvements in progression‐free survival (PFS) and overall survival (OS) for patients randomized to pembrolizumab compared with chemotherapy. In KEYNOTE−024, patients with previously untreated mNSCLC who received pembrolizumab (200 mg intravenously [IV] every 3 weeks) had a statistically significant improvement in OS (hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.41–0.89; p = .005), and significant improvement in PFS (HR 0.50; 95% CI: 0.37–0.68; p < .001). In KEYNOTE‐010, patients with disease progression on or after platinum‐containing chemotherapy received pembrolizumab IV 2 mg/kg, 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks. The HR and p value for OS was 0.71 (95% CI: 0.58–0.88), p < .001 comparing pembrolizumab 2 mg/kg with chemotherapy and the HR and p value for OS was 0.61 (95% CI: 0.49–0.75), p < .001 comparing pembrolizumab 10 mg/kg with chemotherapy. This is the first U.S. Food and Drug Administration approval of a checkpoint inhibitor for first‐line treatment of lung cancer. This approval expands the pembrolizumab indication in second‐line treatment of lung cancer to include all patients with programmed death‐ligand 1‐expressing non‐small cell lung cancer.