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.
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。