Abstract：
OBJECTIVE: Adding immune checkpoint blockade (ICB) to concurrent chemoradiotherapy (cCRT) has improved overall survival (OS) for inoperable locally advanced non-small cell lung cancer. Trials of cCRT-ICB are heterogeneous for factors such as tumor stage and histology, programmed cell death ligand-1 (PDL-1) status, and cCRT-ICB schedules. We therefore aimed to determine the ICB contribution to survival across studies and identify factors associated with survival gain.
METHODS: Data were collated from cCRT-ICB clinical studies published 2018 to 2022 that treated 2196 patients with non-small cell lung cancer (99% stage 3). Associations between 2-year OS and ICB, CRT, patient and tumor factors were investigated using metaregression. A published model of survival after radiation therapy (RT) or CRT was extended to include ICB effects. The model was fitted simultaneously to the cCRT-ICB data and data previously compiled for RT/CRT treatments alone. The net ICB contribution (OS gain) and its associations with factors were described by fitted values of ICB terms added to the model. Statistical significance was determined by likelihood-ratio testing.
RESULTS: The gain in 2-year OS from ICB was 9.9% overall (95% CI, 7.6%, 12.2%; P = .018). Both OS gain and 2-year OS itself rose with increasing planned ICB duration (P = .008, .002, respectively) and with tumor PDL-1 ≥ 1% (P = .034, .023). Fitted OS gains were also greater for patients with stage 3B/C disease (P = .021). OS gain was not associated with tumor histology, patient performance status, radiation therapy dose, ICB drug type (anti-PDL-1 vs anti-programmed cell death-1), or whether ICB began concurrently with or after cCRT.
CONCLUSIONS: Fitted gains in 2-year OS due to ICB were higher in cohorts with greater fractions of stage 3B/C patients and patients with tumor PDL-1 ≥ 1%. OS gain was also significantly higher in a single cohort with a planned ICB duration of 2 years rather than 1, but was not associated with whether ICB treatment began during versus after CRT.
METHODS: Data were collated from cCRT-ICB clinical studies published 2018 to 2022 that treated 2196 patients with non-small cell lung cancer (99% stage 3). Associations between 2-year OS and ICB, CRT, patient and tumor factors were investigated using metaregression. A published model of survival after radiation therapy (RT) or CRT was extended to include ICB effects. The model was fitted simultaneously to the cCRT-ICB data and data previously compiled for RT/CRT treatments alone. The net ICB contribution (OS gain) and its associations with factors were described by fitted values of ICB terms added to the model. Statistical significance was determined by likelihood-ratio testing.
RESULTS: The gain in 2-year OS from ICB was 9.9% overall (95% CI, 7.6%, 12.2%; P = .018). Both OS gain and 2-year OS itself rose with increasing planned ICB duration (P = .008, .002, respectively) and with tumor PDL-1 ≥ 1% (P = .034, .023). Fitted OS gains were also greater for patients with stage 3B/C disease (P = .021). OS gain was not associated with tumor histology, patient performance status, radiation therapy dose, ICB drug type (anti-PDL-1 vs anti-programmed cell death-1), or whether ICB began concurrently with or after cCRT.
CONCLUSIONS: Fitted gains in 2-year OS due to ICB were higher in cohorts with greater fractions of stage 3B/C patients and patients with tumor PDL-1 ≥ 1%. OS gain was also significantly higher in a single cohort with a planned ICB duration of 2 years rather than 1, but was not associated with whether ICB treatment began during versus after CRT.
摘要：
目的：在同步放化疗（cCRT）中加入免疫检查点阻断（ICB）可改善无法手术的局部晚期非小细胞肺癌（LA-NSCLC）的总生存期（OS）。cCRT-ICB的试验在肿瘤分期和组织学等因素上是异质的，PDL1状态和cCRT-ICB计划。因此，我们旨在确定ICB对研究中生存的贡献，并确定与生存增长相关的因素。
方法：数据来自2018-2022年发表的cCRT-ICB临床研究，该研究治疗了2196例NSCLC患者（99％的III期）。两年操作系统和ICB之间的关联，CRT,使用meta回归对患者和肿瘤因素进行调查.已发表的RT或CRT后生存模型被扩展到包括ICB效应。将该模型同时拟合到cCRT-ICB数据和先前单独为RT/CRT治疗编制的数据。通过添加到模型中的ICB项的拟合值来描述净ICB贡献(“OS增益”)及其与因素的关联。通过似然比检验确定统计学显著性。
结果：ICB的2年OS总体收益为9.9％（95％CI：7.6％，12.2%；p=0.018）。OS增益和2年OS本身随着计划ICB持续时间的增加（分别为p=0.008，0.002）和肿瘤PDL1≥1％（p=0.034，0.023）而上升。IIIB/C期患者的OS增益也更高（p=0.021）。OS增加与肿瘤组织学无关，患者表现状况,RT剂量，ICB药物类型（抗PDL1与抗PD1）或ICB是否在cCRT同时或之后开始。
结论：在IIIB/C期患者和肿瘤PDL1≥1%的患者中，由于ICB导致的2年OS的拟合增益更高。在计划的ICB持续时间为两年而不是一年的单个队列中，OS增益也显着更高。但与是否在CRT后开始ICB治疗无关.
方法：数据来自2018-2022年发表的cCRT-ICB临床研究，该研究治疗了2196例NSCLC患者（99％的III期）。两年操作系统和ICB之间的关联，CRT,使用meta回归对患者和肿瘤因素进行调查.已发表的RT或CRT后生存模型被扩展到包括ICB效应。将该模型同时拟合到cCRT-ICB数据和先前单独为RT/CRT治疗编制的数据。通过添加到模型中的ICB项的拟合值来描述净ICB贡献(“OS增益”)及其与因素的关联。通过似然比检验确定统计学显著性。
结果：ICB的2年OS总体收益为9.9％（95％CI：7.6％，12.2%；p=0.018）。OS增益和2年OS本身随着计划ICB持续时间的增加（分别为p=0.008，0.002）和肿瘤PDL1≥1％（p=0.034，0.023）而上升。IIIB/C期患者的OS增益也更高（p=0.021）。OS增加与肿瘤组织学无关，患者表现状况,RT剂量，ICB药物类型（抗PDL1与抗PD1）或ICB是否在cCRT同时或之后开始。
结论：在IIIB/C期患者和肿瘤PDL1≥1%的患者中，由于ICB导致的2年OS的拟合增益更高。在计划的ICB持续时间为两年而不是一年的单个队列中，OS增益也显着更高。但与是否在CRT后开始ICB治疗无关.
