比较治疗既往治疗的晚期或转移性非小细胞肺癌的疗效：网络荟萃分析。

Comparative Efficacy of Treatments for Previously Treated Advanced or Metastatic Non-Small-Cell Lung Cancer: A Network Meta-Analysis.

机构信息

Analysis Group Inc., 111 Huntington Ave, Floor 14, Boston, MA, 02199, USA.

Novartis Pharmaceuticals Corporation, 1 Health Plaza, East Hanover, NJ, 07936, USA.

出版信息

Adv Ther. 2018 Jul;35(7):1035-1048. doi: 10.1007/s12325-018-0734-9. Epub 2018 Jun 15.

DOI:10.1007/s12325-018-0734-9

PMID:29949047

Abstract

INTRODUCTION

Due to the rarity of BRAF V600E mutation, no randomized study has compared the combination targeted therapy dabrafenib + trametinib with other second-line treatments for advanced or metastatic non-small-cell lung cancer (NSCLC). A network meta-analysis (NMA) was conducted to assess the comparative efficacy of treatments among patients with previously treated advanced or metastatic NSCLC.

METHODS

Randomized trials of dabrafenib + trametinib, docetaxel, erlotinib, nintedanib + docetaxel, nivolumab, pemetrexed, pembrolizumab, and best supportive care as second-line or above treatments for advanced or metastatic NSCLC identified in a systematic literature review were included in the NMA. Overall response rates (ORRs) and disease control rates (DCRs) were compared using logit models; progression-free survival (PFS) and overall survival (OS) were compared using fractional polynomial hazards models. Dabrafenib + trametinib was linked into the evidence network through a matching-adjusted indirect comparison versus nivolumab.

RESULTS

Ten trials met the inclusion criteria and were included in the NMA. Dabrafenib + trametinib, pembrolizumab, and nivolumab were associated with the highest odds of achieving overall response (12.2, 1.2, and 0.7 times higher, respectively, compared with docetaxel). Estimated DCR was higher for dabrafenib + trametinib, nintedanib + docetaxel, and pemetrexed compared with other treatments. Patients treated with dabrafenib + trametinib, nivolumab, and pembrolizumab had the lowest hazards of disease progression or death during follow-up (72, 61, and 29% lower hazard of progression at 6 months; 61, 48, and 46% lower hazard of death at 1 year, respectively, compared with docetaxel).

CONCLUSION

Dabrafenib + trametinib, pembrolizumab, and nivolumab were associated with higher ORR and prolonged PFS and OS compared with chemotherapy in previously treated advanced or metastatic NSCLC.

FUNDING

Novartis Pharmaceuticals Corporation.

摘要

简介

由于 BRAF V600E 突变的罕见性，尚无随机研究比较达拉非尼联合曲美替尼与其他二线治疗方案用于晚期或转移性非小细胞肺癌（NSCLC）的疗效。本研究采用网络荟萃分析（NMA）比较了既往治疗的晚期或转移性 NSCLC 患者的不同治疗方案的疗效。

方法

通过系统文献回顾，确定了达拉非尼联合曲美替尼、多西他赛、厄洛替尼、尼达尼布联合多西他赛、纳武单抗、培美曲塞、帕博丽珠单抗和最佳支持治疗作为晚期或转移性 NSCLC 的二线或以上治疗方案的随机试验，纳入 NMA 分析。采用对数模型比较总体缓解率（ORR）和疾病控制率（DCR）；采用分数多项式风险模型比较无进展生存期（PFS）和总生存期（OS）。达拉非尼联合曲美替尼与纳武单抗通过匹配调整间接比较进行连接。

结果

10 项试验符合纳入标准，纳入 NMA 分析。与多西他赛相比，达拉非尼联合曲美替尼、帕博丽珠单抗和纳武单抗的 ORR 更高（分别为 12.2、1.2 和 0.7 倍）。与其他治疗相比，达拉非尼联合曲美替尼、尼达尼布联合多西他赛和培美曲塞的 DCR 更高。在随访期间，接受达拉非尼联合曲美替尼、纳武单抗和帕博丽珠单抗治疗的患者疾病进展或死亡的风险最低（与多西他赛相比，6 个月时疾病进展的风险分别降低了 72%、61%和 29%；1 年时死亡的风险分别降低了 61%、48%和 46%）。