Wang Yu, Zhang Tao, Huang Yilin, Li Wei, Zhao Jingjing, Yang Yin, Li Canjun, Wang Luhua, Bi Nan
Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Division of Prevention and Community Health, National Center for Cardiovascular Disease, National Clinical Research Center of Cardiovascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Int J Radiat Oncol Biol Phys. 2022 Apr 1;112(5):1154-1164. doi: 10.1016/j.ijrobp.2021.12.150. Epub 2021 Dec 26.
Consolidation durvalumab after chemoradiation therapy (CRT) has improved patient outcomes in stage III non-small cell lung cancer (NSCLC) since the practice-changing results of the PACIFIC trial, whereas real-world evidence regarding the PACIFIC regimen has not been systematically reviewed. This meta-analysis comprehensively investigated the real-world toxicity and efficacy of this regimen and identified differences between the real world and clinical trials.
Real-world studies (RWSs) on patients with stage III NSCLC treated with durvalumab after CRT were identified in MEDLINE, EMBASE, PubMed, and Cochrane Library databases. We summarized the differences in demographic and therapeutic characteristics between RWSs and the PACIFIC trial. A meta-analysis of short-term efficacy and adverse event rates was performed. Subgroup analyses were conducted to identify potential influencing factors.
Thirteen studies involving 1885 patients were included. More elderly and poor-performance-status patients, prolonged interval from CRT completion to durvalumab exceeding 42 days, median infusions of durvalumab <20 cycles, and sequential CRT were observed in the real world. The pooled 12-month overall survival (OS) and progression-free survival (PFS) rates were 90% (95% confidence interval [CI], 83%-98%) and 62% (95% CI, 56%-68%), respectively. Subgroup analysis determined that delay in durvalumab initiation beyond 42 days did not affect 12-month OS (P = .068) or PFS (P = .989). Pooled incidences of all-grade and grade ≥3 pneumonitis were 35% (95% CI, 22%-48%) and 6% (95% CI, 3%-8%), respectively. Higher all-grade pneumonitis rates were observed in the studies of patients with a median age of >65 years (P = .008) and from Asian regions (P = .017), whereas expanded access program-related studies reported significantly lower rates (P = .024).
The safety and short-term efficacy of consolidation durvalumab in real-life use aligns with the PACIFIC trial. RWSs can be helpful for understanding the true efficacy and toxicity of consolidation durvalumab given the less-restrictive eligibility criteria.
自PACIFIC试验取得改变实践的结果以来，同步放化疗（CRT）后巩固使用度伐利尤单抗已改善了III期非小细胞肺癌（NSCLC）患者的预后，然而关于PACIFIC方案的真实世界证据尚未得到系统综述。这项荟萃分析全面调查了该方案的真实世界毒性和疗效，并确定了真实世界与临床试验之间的差异。
在MEDLINE、EMBASE、PubMed和Cochrane图书馆数据库中检索关于CRT后接受度伐利尤单抗治疗的III期NSCLC患者的真实世界研究（RWS）。我们总结了RWS与PACIFIC试验在人口统计学和治疗特征方面的差异。对短期疗效和不良事件发生率进行了荟萃分析。进行亚组分析以确定潜在影响因素。
纳入了13项研究，共1885例患者。在真实世界中观察到更多老年和体能状态较差的患者、从CRT完成到度伐利尤单抗的间隔时间延长超过42天、度伐利尤单抗的中位输注次数<20个周期以及序贯CRT。汇总的12个月总生存（OS）率和无进展生存（PFS）率分别为90%（95%置信区间[CI]，83%-98%）和62%（95%CI，56%-68%）。亚组分析确定，度伐利尤单抗开始时间延迟超过42天不影响12个月OS（P = 0.068）或PFS（P = 0.989）。所有级别和≥3级肺炎的汇总发生率分别为35%（95%CI, 22%-48%）和6%（95%CI, 3%-8%）。在中位年龄>65岁的患者研究中（P = 0.008）和亚洲地区的研究中（P = 0.017）观察到更高的所有级别肺炎发生率，而扩大可及项目相关研究报告的发生率显著更低（P = 0.024）。
巩固使用度伐利尤单抗在实际应用中的安全性和短期疗效与PACIFIC试验一致。鉴于入选标准限制较少，RWS有助于理解巩固使用度伐利尤单抗的真实疗效和毒性。
