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Abstract：
BACKGROUND: Part E of the KEYNOTE-011 (NCT01840579) study assessed the safety and antitumor activity of pembrolizumab plus platinum-etoposide chemotherapy in Japanese patients with previously untreated extensive-stage small-cell lung cancer (ES-SCLC).
METHODS: Patients received 4 cycles of pembrolizumab (200 mg) every 3 weeks in combination with cisplatin (75 mg/m2) and etoposide (100 mg/m2; days 1, 2, 3) in cohort 1; with carboplatin (AUC 5 mg/mL/min) and etoposide (100 mg/m2; days 1, 2, 3) in cohort 2; or with cisplatin/etoposide and pegfilgrastim (3.6 mg; cycle 1, day 4) in cohort 3. Combination therapy was followed by pembrolizumab monotherapy (31 cycles). The primary endpoint was safety and tolerability (including dose-limiting toxicities; DLTs).
RESULTS: Fifteen patients were included in the study (cohort 1, n = 6; cohort 2, n = 6; cohort 3, n = 3). Median time from treatment allocation to data cutoff was 22.1 months (range, 4.1‒32.4 months). DLTs occurred in 3 patients in cohort 1 (one patient with grade 4 laryngeal stenosis and grade 3 febrile neutropenia; two patients with grade 3 febrile neutropenia); no patients in cohorts 2 or 3 experienced DLTs. Grade ≥ 3 treatment-related adverse events included leukopenia (67%) and neutropenia (87%). Among all patients, ORR was 67% (95% CI, 38%‒88%) and median DOR was 4.5 months (range, 2.8‒28.8 months). Median PFS was 4.2 months (95% CI, 3.0‒7.8 months) and median OS was 22.1 months (95% CI, 7.4‒25.9 months).
CONCLUSIONS: Pembrolizumab in combination with platinum-etoposide therapy had manageable toxicity with no new safety signals and was associated with antitumor activity in Japanese patients with ES-SCLC.
BACKGROUND: ClinicalTrials.gov , NCT01840579.
METHODS: Patients received 4 cycles of pembrolizumab (200 mg) every 3 weeks in combination with cisplatin (75 mg/m2) and etoposide (100 mg/m2; days 1, 2, 3) in cohort 1; with carboplatin (AUC 5 mg/mL/min) and etoposide (100 mg/m2; days 1, 2, 3) in cohort 2; or with cisplatin/etoposide and pegfilgrastim (3.6 mg; cycle 1, day 4) in cohort 3. Combination therapy was followed by pembrolizumab monotherapy (31 cycles). The primary endpoint was safety and tolerability (including dose-limiting toxicities; DLTs).
RESULTS: Fifteen patients were included in the study (cohort 1, n = 6; cohort 2, n = 6; cohort 3, n = 3). Median time from treatment allocation to data cutoff was 22.1 months (range, 4.1‒32.4 months). DLTs occurred in 3 patients in cohort 1 (one patient with grade 4 laryngeal stenosis and grade 3 febrile neutropenia; two patients with grade 3 febrile neutropenia); no patients in cohorts 2 or 3 experienced DLTs. Grade ≥ 3 treatment-related adverse events included leukopenia (67%) and neutropenia (87%). Among all patients, ORR was 67% (95% CI, 38%‒88%) and median DOR was 4.5 months (range, 2.8‒28.8 months). Median PFS was 4.2 months (95% CI, 3.0‒7.8 months) and median OS was 22.1 months (95% CI, 7.4‒25.9 months).
CONCLUSIONS: Pembrolizumab in combination with platinum-etoposide therapy had manageable toxicity with no new safety signals and was associated with antitumor activity in Japanese patients with ES-SCLC.
BACKGROUND: ClinicalTrials.gov , NCT01840579.
摘要：
背景：KEYNOTE-011（NCT01840579）研究的E部分评估了派姆单抗联合铂-依托泊苷化疗在先前未治疗的广泛期小细胞肺癌（ES-SCLC）日本患者中的安全性和抗肿瘤活性。
方法：患者每3周接受4个周期的pembrolizumab（200mg），与顺铂（75mg/m2）和依托泊苷（100mg/m2；第1、2、3天）联合使用队列1；卡铂（AUC5mg/mL/min）和依托泊苷（100mg/m2；第1、2天，第3天的依托泊联合治疗之后是pembrolizumab单药治疗（31个周期）。主要终点是安全性和耐受性（包括剂量限制性毒性；DLT）。
结果：15例患者纳入研究（队列1，n=6；队列2，n=6；队列3，n=3）。从治疗分配到数据截止的中位时间为22.1个月(范围，4.1-32.4个月）。DLT发生在队列1中的3例患者中（1例4级喉部狭窄和3级发热性中性粒细胞减少症；2例3级发热性中性粒细胞减少症）；队列2或3中没有患者经历DLT。≥3级治疗相关不良事件包括白细胞减少症（67%）和中性粒细胞减少症（87%）。在所有患者中，ORR为67%（95%CI，38%-88%），中位DOR为4.5个月（范围，2.8-28.8个月）。中位PFS为4.2个月（95%CI，3.0-7.8个月），中位OS为22.1个月（95%CI，7.4-25.9个月）。
结论：Pembrolizumab联合铂-依托泊苷治疗具有可控的毒性，没有新的安全性信号，并且与日本ES-SCLC患者的抗肿瘤活性相关。
背景：ClinicalTrials.gov，NCT01840579。
方法：患者每3周接受4个周期的pembrolizumab（200mg），与顺铂（75mg/m2）和依托泊苷（100mg/m2；第1、2、3天）联合使用队列1；卡铂（AUC5mg/mL/min）和依托泊苷（100mg/m2；第1、2天，第3天的依托泊联合治疗之后是pembrolizumab单药治疗（31个周期）。主要终点是安全性和耐受性（包括剂量限制性毒性；DLT）。
结果：15例患者纳入研究（队列1，n=6；队列2，n=6；队列3，n=3）。从治疗分配到数据截止的中位时间为22.1个月(范围，4.1-32.4个月）。DLT发生在队列1中的3例患者中（1例4级喉部狭窄和3级发热性中性粒细胞减少症；2例3级发热性中性粒细胞减少症）；队列2或3中没有患者经历DLT。≥3级治疗相关不良事件包括白细胞减少症（67%）和中性粒细胞减少症（87%）。在所有患者中，ORR为67%（95%CI，38%-88%），中位DOR为4.5个月（范围，2.8-28.8个月）。中位PFS为4.2个月（95%CI，3.0-7.8个月），中位OS为22.1个月（95%CI，7.4-25.9个月）。
结论：Pembrolizumab联合铂-依托泊苷治疗具有可控的毒性，没有新的安全性信号，并且与日本ES-SCLC患者的抗肿瘤活性相关。
背景：ClinicalTrials.gov，NCT01840579。
