Matsumoto Kinnosuke, Shiroyama Takayuki, Kuge Tomoki, Miyake Kotaro, Yamamoto Yuji, Yoneda Midori, Yamamoto Makoto, Naito Yujiro, Suga Yasuhiko, Fukushima Kiyoharu, Koyama Shohei, Iwahori Kota, Hirata Haruhiko, Nagatomo Izumi, Takeda Yoshito, Kumanogoh Atsushi
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.
Lung Cancer. 2021 Dec;162:175-184. doi: 10.1016/j.lungcan.2021.11.008. Epub 2021 Nov 17.
Several studies have demonstrated that anti-angiogenic agents (AAs) have the ability to regulate immune-related cells in the tumor microenvironment and may affect the clinical effect of immune checkpoint inhibitors (ICIs). Therefore, we investigated the drug interaction between ICI and AA for advanced non-small cell lung cancer (NSCLC).
We systematically searched PubMed-MEDLINE, Embase-Scopus, and ISI Web of Science before August 23, 2021. ICI and AA therapy included the concomitant and sequential use of ICIs and AAs. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of patients who received ICI and AA therapy were evaluated and compared to those of patients who received either monotherapy. Subgroup analyses were performed to clarify the cause of heterogeneity; the timing and sequence of ICI and AA administration were predefined as the subgroups.
Thirteen studies involving 2414 patients were included in the meta-analysis. ICI and AA therapy had significantly higher ORR than either monotherapy (OR [95% CI]: 0.61 [0.50-0.74]; p < 0.001; I = 29%). PFS and OS were favorable benefits in ICI and AA therapy; however, significant heterogeneity was identified in these analyses (I = 80% and 59%, respectively). According to the administration timing and sequence, ICI immediately after AA showed no PFS and OS benefits compared to ICI monotherapy (HR [95 % CI]: 1.54 [1.14-2.08] and 1.50 [1.04-2.15], respectively), whereas favorable PFS and OS were demonstrated when AA was concomitantly administered with ICI (HR [95 % CI]: 0.57 [0.43-0.76] and 0.80 [0.61-1.05], respectively) or when AA was administered immediately after ICI (HR [95 % CI]: 0.58 [0.34-1.00] and 0.56 [0.40-0.80], respectively).
ICI and AA therapy can provide favorable clinical effects compared to either monotherapy; however, ICI administered immediately after AA may not show survival benefits.
多项研究表明，抗血管生成药物（AAs）有能力调节肿瘤微环境中与免疫相关的细胞，并可能影响免疫检查点抑制剂（ICIs）的临床疗效。因此，我们研究了ICI与AA联合治疗晚期非小细胞肺癌（NSCLC）的药物相互作用。
我们于2021年8月23日前系统检索了PubMed-MEDLINE、Embase-Scopus和ISI科学网。ICI和AA治疗包括ICIs与AAs的联合使用和序贯使用。评估接受ICI和AA治疗患者的客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS），并与接受单一疗法的患者进行比较。进行亚组分析以阐明异质性的原因；将ICI和AA给药的时间和顺序预先定义为亚组。
荟萃分析纳入了13项涉及2414例患者的研究。ICI和AA联合治疗的ORR显著高于单一疗法（OR [95% CI]：0.61 [0.50 - 0.74]；p < 0.001；I² = 29%）。PFS和OS在ICI和AA联合治疗中是有益的；然而，在这些分析中发现了显著的异质性（I²分别为80%和59%）。根据给药时间和顺序，与ICI单一疗法相比，AA后立即给予ICI未显示出PFS和OS获益（HR [95% CI]：分别为1.54 [1.14 - 2.08]和1.50 [1.04 - 2.15]），而当AA与ICI同时给药（HR [95% CI]：分别为0.57 [0.43 - 0.76]和0.80 [0.61 - 1.05]）或在ICI后立即给予AA（HR [95% CI]：分别为0.58 [0.34 - 1.00]和0.56 [0.40 - 0.80]）时，显示出良好的PFS和OS。
与单一疗法相比，ICI和AA联合治疗可提供良好的临床效果；然而，在AA后立即给予ICI可能未显示出生存获益。
