Abstract：
BACKGROUND: We report long-term outcomes from a pooled analysis of patients with previously untreated metastatic NSCLC with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) less than 1% enrolled in phase III studies of pembrolizumab plus chemotherapy versus placebo plus chemotherapy.
METHODS: This exploratory pooled analysis included individual patient data from the KEYNOTE-189 global (NCT02578680) and Japan extension (NCT03950674) studies of metastatic nonsquamous NSCLC without EGFR or ALK alterations and the KEYNOTE-407 global (NCT02775435) and People\'s Republic of China extension (NCT03875092) studies of metastatic squamous NSCLC. Patients received pembrolizumab or placebo plus pemetrexed and cisplatin or carboplatin in KEYNOTE-189 and pembrolizumab or placebo plus carboplatin and paclitaxel or nab-paclitaxel in KEYNOTE-407. PD-L1 TPS was centrally assessed using PD-L1 IHC 22C3 pharmDx (Agilent Technologies, Carpinteria, CA).
RESULTS: Overall, 442 patients were included in this analysis (pembrolizumab plus chemotherapy, n = 255; chemotherapy, n = 187). The median follow-up was 60.7 (range, 49.9‒72.0) months. Pembrolizumab plus chemotherapy improved overall survival (hazard ratio, 0.64; 95% confidence interval [CI]: 0.51‒0.79) and progression-free survival (hazard ratio, 0.66; 95% CI: 0.54‒0.81) versus chemotherapy. The 5-year overall survival rates (95% CI) were 12.5% (8.6%‒17.3%) versus 9.3% (5.6%‒14.1%). Grades 3 to 5 treatment-related adverse events occurred in 59.1% of patients for pembrolizumab plus chemotherapy and 61.3% for chemotherapy.
CONCLUSIONS: With approximately 5 years of follow-up, pembrolizumab plus chemotherapy provided clinically meaningful and durable improvements in survival outcomes versus chemotherapy alone in patients with previously untreated metastatic NSCLC with PD-L1 TPS less than 1%. These results continue to support pembrolizumab plus chemotherapy as a standard of care in this patient population.
RESULTS: gov, NCT02578680 (KEYNOTE-189 global), NCT03950674 (KEYNOTE-189 Japan extension), NCT02775435 (KEYNOTE-407 global), NCT03875092 (KEYNOTE-407 People\'s Republic of China extension).
METHODS: This exploratory pooled analysis included individual patient data from the KEYNOTE-189 global (NCT02578680) and Japan extension (NCT03950674) studies of metastatic nonsquamous NSCLC without EGFR or ALK alterations and the KEYNOTE-407 global (NCT02775435) and People\'s Republic of China extension (NCT03875092) studies of metastatic squamous NSCLC. Patients received pembrolizumab or placebo plus pemetrexed and cisplatin or carboplatin in KEYNOTE-189 and pembrolizumab or placebo plus carboplatin and paclitaxel or nab-paclitaxel in KEYNOTE-407. PD-L1 TPS was centrally assessed using PD-L1 IHC 22C3 pharmDx (Agilent Technologies, Carpinteria, CA).
RESULTS: Overall, 442 patients were included in this analysis (pembrolizumab plus chemotherapy, n = 255; chemotherapy, n = 187). The median follow-up was 60.7 (range, 49.9‒72.0) months. Pembrolizumab plus chemotherapy improved overall survival (hazard ratio, 0.64; 95% confidence interval [CI]: 0.51‒0.79) and progression-free survival (hazard ratio, 0.66; 95% CI: 0.54‒0.81) versus chemotherapy. The 5-year overall survival rates (95% CI) were 12.5% (8.6%‒17.3%) versus 9.3% (5.6%‒14.1%). Grades 3 to 5 treatment-related adverse events occurred in 59.1% of patients for pembrolizumab plus chemotherapy and 61.3% for chemotherapy.
CONCLUSIONS: With approximately 5 years of follow-up, pembrolizumab plus chemotherapy provided clinically meaningful and durable improvements in survival outcomes versus chemotherapy alone in patients with previously untreated metastatic NSCLC with PD-L1 TPS less than 1%. These results continue to support pembrolizumab plus chemotherapy as a standard of care in this patient population.
RESULTS: gov, NCT02578680 (KEYNOTE-189 global), NCT03950674 (KEYNOTE-189 Japan extension), NCT02775435 (KEYNOTE-407 global), NCT03875092 (KEYNOTE-407 People\'s Republic of China extension).
摘要：
背景：我们报告了一项汇总分析的长期结果，该分析对先前未经治疗的转移性非小细胞肺癌（NSCLC）患者进行了程序性细胞死亡配体1（PD-L1）肿瘤比例评分（TPS）<1％的患者进行了Pembrolizumab联合化疗与安慰剂联合化疗的3期研究。
方法：这项探索性汇总分析包括来自KEYNOTE-189全球（NCT02578680）和日本扩展（NCT03950674）的无EGFR或ALK改变的转移性非鳞状细胞肺癌研究的个体患者数据，以及KEYNOTE-407全球（NCT02775435）和中国扩展（NCT03875092）的转移性鳞状细胞肺癌研究。患者在KEYNOTE-189中接受派姆单抗或安慰剂加培美曲塞和顺铂或卡铂，在KEYNOTE-407中接受派姆单抗或安慰剂加卡铂和紫杉醇或nab-紫杉醇。PD-L1TPS使用PD-L1IHC22C3制药X(安捷伦技术，Carpinteria,CA).
结果：总体而言，442例患者被纳入本分析(pembrolizumab+化疗，n=255；化疗，n=187）。中位随访为60.7(范围，49.9-72.0）个月。Pembrolizumab联合化疗改善了总生存率（OS；风险比[HR]，0.64；95%CI，0.51~0.79）和无进展生存期（HR，0.66；95%CI，0.54-0.81）与化疗。五年OS率（95%CI）分别为12.5%（8.6%-17.3%）和9.3%（5.6%-14.1%）。3-5级治疗相关的不良事件发生在59.1%的患者中，pembrolizumab加化疗和61.3%的患者中。
结论：经过5年的随访，在先前未治疗的PD-L1TPS<1%的转移性NSCLC患者中,与单纯化疗相比,派姆单抗联合化疗在生存结局方面提供了有临床意义且持久的改善.这些结果继续支持pembrolizumab加化疗作为该患者群体的标准治疗。
方法：这项探索性汇总分析包括来自KEYNOTE-189全球（NCT02578680）和日本扩展（NCT03950674）的无EGFR或ALK改变的转移性非鳞状细胞肺癌研究的个体患者数据，以及KEYNOTE-407全球（NCT02775435）和中国扩展（NCT03875092）的转移性鳞状细胞肺癌研究。患者在KEYNOTE-189中接受派姆单抗或安慰剂加培美曲塞和顺铂或卡铂，在KEYNOTE-407中接受派姆单抗或安慰剂加卡铂和紫杉醇或nab-紫杉醇。PD-L1TPS使用PD-L1IHC22C3制药X(安捷伦技术，Carpinteria,CA).
结果：总体而言，442例患者被纳入本分析(pembrolizumab+化疗，n=255；化疗，n=187）。中位随访为60.7(范围，49.9-72.0）个月。Pembrolizumab联合化疗改善了总生存率（OS；风险比[HR]，0.64；95%CI，0.51~0.79）和无进展生存期（HR，0.66；95%CI，0.54-0.81）与化疗。五年OS率（95%CI）分别为12.5%（8.6%-17.3%）和9.3%（5.6%-14.1%）。3-5级治疗相关的不良事件发生在59.1%的患者中，pembrolizumab加化疗和61.3%的患者中。
结论：经过5年的随访，在先前未治疗的PD-L1TPS<1%的转移性NSCLC患者中,与单纯化疗相比,派姆单抗联合化疗在生存结局方面提供了有临床意义且持久的改善.这些结果继续支持pembrolizumab加化疗作为该患者群体的标准治疗。
