Phase 1 study of pembrolizumab plus chemotherapy in Japanese patients with extensive-stage small-cell lung cancer.

IF 3 3区医学 Q2 ONCOLOGY

Investigational New Drugs Pub Date : 2024-02-01 DOI:10.1007/s10637-023-01411-1

Naoyuki Nogami, Takaaki Tokito, Yoshitaka Zenke, Miyako Satouchi, Takashi Seto, Hideo Saka, Junko Ohtani, Shirong Han, Kazuo Noguchi, Makoto Nishio

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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).

Conclusion: 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.

Trial registration: ClinicalTrials.gov , NCT01840579.

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针对日本广泛期小细胞肺癌患者的 pembrolizumab 加化疗的 1 期研究。

研究背景KEYNOTE-011（NCT01840579）研究的E部分评估了pembrolizumab联合铂-依托泊苷化疗对既往未经治疗的广泛期小细胞肺癌（ES-SCLC）日本患者的安全性和抗肿瘤活性：第一组患者每3周接受4个周期的pembrolizumab（200毫克）联合顺铂（75毫克/平方米）和依托泊苷（100毫克/平方米；第1、2、3天）治疗；第二组患者接受卡铂（AUC 5毫克/毫升/分钟）和依托泊苷（100毫克/平方米；第1、2、3天）治疗；第三组患者接受顺铂/依托泊苷和pegfilgrastim（3.6毫克；第1周期，第4天）治疗。联合治疗后进行 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；DLTs）：研究共纳入15名患者（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（4.1-32.4 个月）。队列1中有3名患者出现了DLT（1名患者出现4级喉狭窄和3级发热性中性粒细胞减少症；2名患者出现3级发热性中性粒细胞减少症）；队列2或队列3中没有患者出现DLT。≥3级的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（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）：Pembrolizumab与铂类-依托泊苷联合治疗的毒性可控，无新的安全性信号，在日本ES-SCLC患者中具有抗肿瘤活性：试验注册：ClinicalTrials.gov , NCT01840579。

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来源期刊

Investigational New Drugs 医学-药学

CiteScore

7.60

自引率

0.00%

发文量

121

审稿时长

1 months

期刊介绍： The development of new anticancer agents is one of the most rapidly changing aspects of cancer research. Investigational New Drugs provides a forum for the rapid dissemination of information on new anticancer agents. The papers published are of interest to the medical chemist, toxicologist, pharmacist, pharmacologist, biostatistician and clinical oncologist. Investigational New Drugs provides the fastest possible publication of new discoveries and results for the whole community of scientists developing anticancer agents.