A phase II study of pembrolizumab and paclitaxel in patients with relapsed or refractory small-cell lung cancer
A phase II study of pembrolizumab and paclitaxel in patients with relapsed or refractory small-cell lung cancer
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DOI：
10.1016/j.lungcan.2019.08.031
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发表时间：
2019-10-01
期刊：
影响因子：
5.3
通讯作者：
Heo, Dae Seog
中科院分区：
文献类型：
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作者：
Kim, Yu-Jung;Keam, Bhumsuk;Heo, Dae Seog
目的：依托泊苷/铂类难治性广泛病灶（ED）小细胞肺癌（SCLC）患者的预后较差。我们的目的是评估派姆单抗和紫杉醇联合治疗对这些患者的疗效和安全性。 方法：在这项多中心、II 期研究中，依托泊苷/铂类化疗后出现进展的 ED-SCLC 患者每 3 周接受 175 mg/m(2) 紫杉醇治疗，最多 6 个周期。从第二个周期开始添加帕博利珠单抗 200 mg，并持续直至疾病进展或出现不可接受的毒性。主要终点是客观缓解率（ORR），次要终点是无进展生存期（PFS）、总生存期（OS）、安全性和生物标志物分析，包括程序性死亡配体1（PD-L1）表达、下一代测序和外周血细胞流式细胞术分析。 结果：在入组的26名患者中，确认的ORR为23.1%（95%CI：6.9%-39.3%）；完全缓解：3.9%，确认部分缓解[PR]：19.2%，疾病稳定：57.7%，疾病进展：7.7%，不可评估：11.5%。包括4例未经证实的PR，患者有效率为38.5%，疾病控制率为80.7%。中位 PFS 和 OS 分别为 5.0 个月（95% CI：2.7-6.7）和 9.1 个月（95% CI：6.5-15.0）。观察到的3级或4级不良事件包括发热性中性粒细胞减少症(7.7%)、中性粒细胞减少症(7.7%)、乏力(7.7%)、低钠血症(7.7%)和I型糖尿病(7.7%)。靶向基因测序未发现与治疗相关的特定基因改变，除了 MET 拷贝数增加（PFS 10.5 与 3.4 个月，p = 0.019）。结论：派姆单抗和紫杉醇联合治疗在难治性 ED-SCLC 患者中显示出中等活性和可接受的毒性。
Objective: Patients with etoposide/platinum-refractory extensive disease (ED) small-cell lung cancer (SCLC) have a dismal prognosis. We aimed to evaluate the efficacy and safety of pembrolizumab and paclitaxel combination therapy in these patients.Methods: In this multi-center, phase II study, ED-SCLC patients who showed progression after etoposide/platinum chemotherapy received paclitaxel 175 mg/m(2) every 3 weeks for up to six cycles. Pembrolizumab 200 mg was added from the second cycle and continued until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS), safety, and biomarker analyses including programmed death-ligand 1 (PD-L1) expression, next-generation sequencing, and flow cytometric analysis of peripheral blood cells.Results: Of the 26 patients enrolled, the confirmed ORR was 23.1% (95%CI: 6.9%-39.3%); complete response: 3.9%, confirmed partial response [PR]: 19.2%, stable disease: 57.7%, progressive disease: 7.7%, and not evaluable: 11.5%. Including 4 cases of unconfirmed PRs, 38.5% of patients were responding and the disease control rate was 80.7%. The median PFS and OS were 5.0 months (95% CI: 2.7-6.7) and 9.1 months (95% CI: 6.5-15.0), respectively. The grade 3 or 4 adverse events observed included febrile neutropenia (7.7%), neutropenia (7.7%), asthenia (7.7%), hyponatremia (7.7%), and type I diabetes (7.7%). Targeted gene sequencing identified no specific genetic alterations correlated with the treatment, except for theMET copy number gain (PFS 10.5 versus 3.4 months, p = 0.019).Conclusions: Pembrolizumab and paclitaxel combination therapy showed a moderate activity with acceptable toxicity in patients with refractory ED-SCLC.