Balasubramanian Adithya, Onggo James, Gunjur Ashray, John Thomas, Parakh Sagun
Department of Medical Oncology, Monash Health, Melbourne, Victoria, Australia.
Department of Surgery, Eastern Health, Melbourne, Victoria, Australia.
Clin Lung Cancer. 2021 Mar;22(2):74-82. doi: 10.1016/j.cllc.2020.10.023. Epub 2020 Nov 12.
The role of immune checkpoint inhibitors (ICIs) administered concurrently with or after definitive chemoradiation (CRT) in stage III non-small-cell lung cancer (NSCLC) has been detailed in several studies. We performed a systematic review to determine pneumonitis rates using ICIs with CRT. MEDLINE and EMBASE databases were searched using keywords and MeSH terms. Studies using anti-programmed cell death protein 1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) therapy, either sequentially or concurrently with CRT, for patients with stage III NSCLC were included. A meta-analysis of pneumonitis rates was performed based on weighted pooled proportion, using random-effects models. Weighting was performed by the inverse variance or standard error of event rates. Comparative analysis between groups was performed. Odds ratios (OR) were used as the primary summary statistics. A total of 13 studies were identified (6 prospective clinical trials and 7 real-world reports). Rates of grade ≥ 3 pneumonitis were significantly higher in clinical trials using anti-PD-1 therapy compared with PD-L1 inhibitors (8.6%; 95% confidence interval [CI], 6.2%-11.9% vs. 4.4%; 95% CI, 3.0%-6.6%; OR, 2.0; P = .01). Clinical trials using concurrent ICI therapy with CRT had greater rates of grade 2 pneumonitis compared with sequential administration (23.0%; 95% CI, 15.8%-32.3% vs. 11.0%; 95% CI, 6.6%-17.8%; OR, 0.42; P = .02). Higher rates of grade ≥ 3 pneumonitis were observed in real-world studies compared with clinical trials involving sequential PD-L1 therapy (9.9%; 95% CI, 5.3%-17.9% vs. 4.4%; 95% CI, 2.9%-6.7%; OR, 0.43; P < .01). The suggestion of increased pneumonitis with a concurrent ICI strategy and using anti-PD-1 therapies warrants further consideration in future comparative studies.
免疫检查点抑制剂（ICI）在III期非小细胞肺癌（NSCLC）的根治性放化疗（CRT）期间或之后使用的作用已在多项研究中详细阐述。我们进行了一项系统评价，以确定使用ICI联合CRT时的肺炎发生率。使用关键词和医学主题词（MeSH）检索MEDLINE和EMBASE数据库。纳入了对III期NSCLC患者使用抗程序性细胞死亡蛋白1（PD-1）或抗程序性死亡配体1（PD-L1）疗法（与CRT序贯或同时使用）的研究。基于加权合并比例，使用随机效应模型对肺炎发生率进行荟萃分析。权重通过事件发生率的逆方差或标准误差进行计算。进行组间比较分析。比值比（OR）用作主要汇总统计量。共确定了13项研究（6项前瞻性临床试验和7项真实世界报告）。与使用PD-L1抑制剂的临床试验相比，使用抗PD-1疗法的临床试验中≥3级肺炎的发生率显著更高（8.6%；95%置信区间[CI]，6.2%-11.9%对4.4%；95%CI，3.0%-6.6%；OR，2.0；P = 0.01）。与序贯给药相比，使用ICI联合CRT的临床试验中2级肺炎的发生率更高（23.0%；95%CI，15.8%-32.3%对11.0%；95%CI，6.6%-17.8%；OR，0.42；P = 0.02）。与涉及序贯PD-L1治疗的临床试验相比，真实世界研究中观察到≥3级肺炎的发生率更高（9.9%；95%CI，5.3%-17.9%对4.4%；95%CI，2.9%-6.7%；OR，0.43；P < 0.01）。关于联合ICI策略和使用抗PD-1疗法会增加肺炎发生率的这一提示值得在未来的比较研究中进一步考虑。
