Duke University Medical Center, Durham, North Carolina.
Massachusetts General Hospital, Boston, Massachusetts.
J Thorac Oncol. 2019 Feb;14(2):237-244. doi: 10.1016/j.jtho.2018.10.003. Epub 2018 Oct 10.
For patients with recurrent SCLC, topotecan remains the only approved second-line treatment, and the outcomes are poor. CheckMate 032 is a phase 1/2, multicenter, open-label study of nivolumab or nivolumab plus ipilimumab in SCLC or other advanced/metastatic solid tumors previously treated with one or more platinum-based chemotherapies. We report results of third- or later-line nivolumab monotherapy treatment in SCLC.
In this analysis, patients with limited-stage or extensive-stage SCLC and disease progression after two or more chemotherapy regimens received nivolumab monotherapy, 3 mg/kg every 2 weeks, until disease progression or unacceptable toxicity. The primary end point was objective response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety.
Between December 4, 2013, and November 30, 2016, 109 patients began receiving third- or later-line nivolumab monotherapy. At a median follow-up of 28.3 months (from first dose to database lock), the objective response rate was 11.9% (95% confidence interval: 6.5-19.5) with a median duration of response of 17.9 months (range 3.0-42.1). At 6 months, 17.2% of patients were progression-free. The 12-month and 18-month overall survival rates were 28.3% and 20.0%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 11.9% of patients. Three patients (2.8%) discontinued because of treatment-related adverse events.
Nivolumab monotherapy provided durable responses and was well tolerated as a third- or later-line treatment for recurrent SCLC. These results suggest that nivolumab monotherapy is an effective third- or later-line treatment for this patient population.
对于复发性 SCLC 患者，拓扑替康仍然是唯一批准的二线治疗药物，但其疗效较差。CheckMate 032 是一项 1/2 期、多中心、开放性研究，评估纳武单抗或纳武单抗联合伊匹单抗治疗既往接受过一种或多种铂类化疗的 SCLC 或其他晚期/转移性实体瘤患者的疗效。我们报告了 SCLC 三线或后线纳武单抗单药治疗的结果。
在这项分析中，局限期或广泛期 SCLC 患者，在接受两种或更多种化疗方案后疾病进展，接受纳武单抗单药治疗，剂量为 3mg/kg，每 2 周 1 次，直至疾病进展或出现不可耐受的毒性。主要终点为客观缓解率。次要终点包括缓解持续时间、无进展生存期、总生存期和安全性。
2013 年 12 月 4 日至 2016 年 11 月 30 日，109 例患者开始接受三线或后线纳武单抗单药治疗。中位随访 28.3 个月（从首次给药至数据库锁定），客观缓解率为 11.9%（95%置信区间：6.5-19.5），缓解持续时间的中位数为 17.9 个月（范围 3.0-42.1）。6 个月时，17.2%的患者无疾病进展。12 个月和 18 个月的总生存率分别为 28.3%和 20.0%。3-4 级与治疗相关的不良事件发生率为 11.9%。有 3 例患者（2.8%）因治疗相关不良事件停药。
纳武单抗单药治疗作为复发性 SCLC 的三线或后线治疗，可产生持久的缓解且耐受良好。这些结果表明，纳武单抗单药治疗是该患者人群的一种有效三线或后线治疗方法。
