不可切除的 III 期表皮生长因子受体（EGFR）突变型非小细胞肺癌治疗方案的比较
Comparison of treatment regimens for unresectable stage III epidermal growth factor receptor ( EGFR ) mutant non-small cell lung cancer.
作者信息
Dai Xin, Xu Qian, Sheng Lei, Zhang Xue, Huang Miao, Li Song, Huang Kai, Chu Jiahui, Wang Jian, Li Jisheng, Liu Yanguo, Zhou Jianyuan, Nie Shulun, Liu Lian
机构信息
Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
Department of Medical Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250011, China.
出版信息
Chin Med J (Engl). 2025 Jul 20;138(14):1687-1695. doi: 10.1097/CM9.0000000000003386. Epub 2024 Dec 6.
BACKGROUND
Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen.
METHODS
We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints.
RESULTS
A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis.
CONCLUSIONS
For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy.
REGISTRATION
PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
背景
在 PACIFIC 研究（评估度伐利尤单抗用于同步放化疗后未出现疾病进展的 III 期不可切除非小细胞肺癌患者）中，放化疗（CRT）后使用度伐利尤单抗未能给表皮生长因子受体（EGFR）突变患者带来生存获益。我们旨在探讨局部晚期不可手术的 EGFR 突变患者是否能从酪氨酸激酶抑制剂（TKIs）中获益以及最佳治疗方案。
方法
我们检索了 PubMed、Embase、Cochrane 对照试验中心注册库和 ClinicalTrials.gov 数据库，检索时间从数据库建立至 2022 年 12 月 31 日，并基于贝叶斯框架进行荟萃分析，将无进展生存期（PFS）和总生存期（OS）作为主要终点。
结果
16 项研究共纳入 1156 例患者，这些研究包括 6 种治疗措施，即 CRT、CRT 后接度伐利尤单抗（CRT-Durva）、TKI 单药治疗、放疗联合 TKI（RT-TKI）、CRT 联合 TKI（CRT-TKI）以及 TKI 联合度伐利尤单抗（TKI-Durva）。接受含 TKI 方案治疗的患者的 PFS 显著长于接受不含 TKI 方案治疗的患者（风险比[HR]=0.37，95%置信区间[CI]，0.20 - 0.66）。TKI 单药治疗的 PFS 显著长于 CRT（HR = 0.66，95%CI，0.50 - 0.87），但短于 RT-TKI（HR = 1.78，95%CI，1.17 - 2.67）。此外，RT-TKI 或 CRT-TKI 的 PFS 均显著长于 CRT 或 CRT-Durva。在综合分析中，RT-TKI 在贝叶斯排名中位列第一，OS 最长（60.8 个月，95%CI = 37.2 - 84.3 个月），PFS 最长（21.5 个月，95%CI，15.4 - 27.5 个月）。
结论
对于不可切除的 III 期 EGFR 突变非小细胞肺癌，放疗和 TKI 均必不可少。基于目前的证据，RT-TKI 带来了更优的生存优势，而 CRT-TKI 需要进一步评估。迫切需要开展大型随机临床试验以探索 TKI、放疗和化疗的合适应用顺序。
注册信息
PROSPERO；https://www.crd.york.ac.uk/PROSPERO/；编号 CRD42022298490。
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