University of Kentucky Markey Cancer Center, Lexington, KY; Division of Medical Oncology, Department of Medicine, University of Kentucky, Lexington, KY.
Cancer Research and Biostatistics, Seattle, WA.
Clin Lung Cancer. 2020 Jul;21(4):357-364.e7. doi: 10.1016/j.cllc.2020.01.006. Epub 2020 Jan 27.
The purpose of this study was to evaluate the efficacy and tolerability of carfilzomib plus irinotecan (C/I) in patients with relapsed small-cell lung cancer (SCLC).
Patients with SCLC who progressed after 1 platinum-containing regimen for recurrent or metastatic disease were eligible. Patients were stratified as: sensitive (SS) (progressive disease > 90 days after chemotherapy) or refractory (RS) (progressive disease 30 to 90 days after chemotherapy) and received up to 6 cycles of C/I; imaging was performed every 2 cycles. The primary endpoint was 6-month overall survival (OS).
All 62 patients enrolled were evaluable for efficacy and adverse events. 6-month OS was 59% in the platinum SS and 54% in the platinum RS. The overall response rate was 21.6% (2.7% complete response, 18.9% partial response) in SS (n = 37) and 12.5% (all partial response) in RS (n = 25). The disease control rate was 68% (SS) and 56% (RS). Progression-free survival and OS were 3.6 months (95% confidence interval [CI], 2.6-4.6 months) and 6.9 months (95% CI, 4.3-12.3 months) in SS, and 3.3 months (95% CI, 1.8-3.9 months) and 6.8 months (95% CI, 4.1-11 months) in RS. Twenty-nine (47%) patients experienced ≥ grade 3 adverse events; 8 (12.9%) subjects had grade 4 toxicities. Three treatment-related deaths occurred: myocardial infarction (possible), lung infection (possible), and sepsis (probable).
In patients with relapsed SCLC, C/I was effective in the treatment of SS and RS. With 4.8% grade 5 toxicity, C/I is a viable option for relapsed patients with SCLC with performance status 0 to 1, particularly in platinum-resistant patients, or subjects who cannot receive immunotherapy.
本研究旨在评估卡非佐米联合伊立替康（C/I）在复发性小细胞肺癌（SCLC）患者中的疗效和耐受性。
本研究纳入了经含铂方案治疗后疾病进展的 SCLC 患者。患者按以下标准分层：敏感型（SS）（化疗后疾病进展时间>90 天）或耐药型（RS）（化疗后疾病进展时间 30-90 天），并接受最多 6 个周期的 C/I 治疗；每 2 个周期进行一次影像学检查。主要终点为 6 个月总生存率（OS）。
本研究共纳入 62 例患者，所有患者均具有疗效和不良事件评估价值。在铂类敏感型（SS）和铂类耐药型（RS）患者中，6 个月 OS 率分别为 59%和 54%。SS 患者的总缓解率为 21.6%（完全缓解率 2.7%，部分缓解率 18.9%），RS 患者的总缓解率为 12.5%（均为部分缓解）。疾病控制率分别为 68%（SS）和 56%（RS）。SS 患者的无进展生存期和 OS 分别为 3.6 个月（95%CI，2.6-4.6 个月）和 6.9 个月（95%CI，4.3-12.3 个月），RS 患者的无进展生存期和 OS 分别为 3.3 个月（95%CI，1.8-3.9 个月）和 6.8 个月（95%CI，4.1-11 个月）。29 例（47%）患者发生≥3 级不良事件；8 例（12.9%）患者发生 4 级毒性。有 3 例治疗相关死亡：心肌梗死（可能）、肺部感染（可能）和脓毒症（可能）。
在复发性 SCLC 患者中，C/I 对 SS 和 RS 均具有治疗效果。C/I 的 5 级毒性发生率为 4.8%，对于体力状况 0-1 分的复发性 SCLC 患者，特别是铂类耐药患者或无法接受免疫治疗的患者，C/I 是一种可行的选择。
