Guo Long-Hua, Zhang Ming-Feng, Zhang He-Long, Zhou Jian-Ying, Cai Xiao-Hong, Long Yu, Guo Qi-Sen, Yang Nong, Zhao Jun, Xie Zhan-Hong, Jiang Bo, Zhu Ying, Fan Yun, Xie Cong-Ying, Hu Yi, Yao Yu, Jia Jun, Li Xiao-Ling, Cui Jiu-Wei, Sui Xi-Zhao, Lin Wen, Cheng Ying, Wang Hui-Juan, Wang Chang-Li, Zhao Ming-Fang, Qiao Gui-Bin, Peng Li-Jun, Yang Lin, Chen Gong-Yan, Cai Kai-Can, Xu Xin-Hua, Zhang Liang-Ming, Feng Guo-Sheng, Zhou Jing-Min, Wu Guo-Wu, Dong Xiao-Rong, Wang Li-Feng, Zhang Hong-Mei, Gao Ya-Jie, Jiang Qiu-Ying, Cang Shun-Dong, Yang Zhi-Xiong, Song Xia, Liu Xiao-Qing, Zhu Bo, Chen Feng-Xia, Hu Chun-Hong, Chen Xi, Wu Yi-Long, Zhou Qing
Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-Sen University, Meizhou, China.
Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China.
Front Oncol. 2020 Sep 15;10:1568. doi: 10.3389/fonc.2020.01568. eCollection 2020.
This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. We retrospectively collected patients ( = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT ( = 0.403, < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: (54.5%), (50.0%), (18.2%), and (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with , and mutations, while mutation was observed only in the DOT ≤ 6.9 months set. This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.
本研究调查了接受培美曲塞一线化疗的部分中国晚期肺腺癌患者的生存情况。我们还探讨了基因生物标志物与培美曲塞疗效之间的关系。我们回顾性收集了2014年11月至2017年6月期间多个中心参与中国患者援助项目的患者(n = 1047),这些患者接受了单独的培美曲塞或联合铂类作为晚期肺腺癌的一线化疗,并继续接受培美曲塞维持治疗。观察指标为治疗持续时间(DOT)和总生存期(OS)。分析临床特征对治疗效果和预后的影响。采用二代测序(NGS)来鉴定与培美曲塞疗效相关的基因生物标志物。中位DOT为9.1个月(95%CI:8.5 - 9.8),中位OS为26.2个月(95%CI:24.2 - 28.1)。OS与DOT呈正相关(r = 0.403,P < 0.001)。多变量分析显示,吸烟状态和东部肿瘤协作组(ECOG)体能状态(PS)与DOT独立相关;吸烟状态、ECOG PS、靶向治疗和KRAS状态与OS独立相关。对22例有可用样本的患者进行NGS检测,显示高突变率的基因有:EGFR(54.5%)、KRAS(50.0%)、NRAS(18.2%)和BRAF(13.6%)。根据PARAMOUNT研究中报道的无进展生存期(PFS)进行分组时,DOT > 6.9个月组与EGFR和NRAS突变相关,而KRAS突变仅在DOT≤6.9个月组中观察到。本研究表明,培美曲塞一线化疗对于部分中国晚期肺腺癌患者是一种有效的治疗方案。通过NGS未发现预测培美曲塞获益的特定基因谱。预测培美曲塞疗效的生物标志物需要进一步探索。