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Efficacy and safety of immune checkpoint inhibitors with or without radiotherapy in metastatic non-small cell lung cancer: A systematic review and meta-analysis.

作者信息

Liu Zijing, Xu Tiankai, Chang Pengyu, Fu Weijia, Wei Jiaying, Xia Chengcheng, Wang Qiang, Li Man, Pu Xiaoyu, Huang Fuxue, Ge Chao, Gao Yan, Gong Shouliang, Liu Chengjiang, Dong Lihua

机构信息

Jilin Provincial Key Laboratory of Radiation Oncology and Therapy, The First Hospital of Jilin University, Changchun, China.

Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, China.

出版信息

Front Pharmacol. 2023 Jan 24;14:1064227. doi: 10.3389/fphar.2023.1064227. eCollection 2023.


DOI:10.3389/fphar.2023.1064227
PMID:36762107
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9902364/
Abstract

Although immune checkpoint inhibitors (ICIs) have become the first-line treatment for metastatic non-small cell lung cancer (mNSCLC), their efficacy is limited. Meanwhile, recent reports suggest that radiotherapy (RT) can activate the systemic antitumor immune response by increasing the release of antigens from tumor tissues. Therefore, in patients with mNSCLC treated with ICIs, investigations were performed to determine whether the addition of RT improved the outcomes. Furthermore, the adverse events rate was evaluated. Pubmed, Embase, and Cochrane Library were searched using the keywords "radiotherapy," "immune checkpoint inhibitors," and "non-small cell lung cancer" from the date of inception to 2 May 2022. Randomized controlled trials (RCTs) and nonRCTs (NRCTs) comparing the efficacy and safety of RT combined with ICIs ICIs alone in metastatic NSCLC were assessed. The primary outcomes were progression-free survival (PFS) and overall survival (OS), and the secondary outcomes were abscopal response rate (ARR), abscopal control rate (ACR), adverse events rate, and pneumonia rate. The analyses were conducted using the Mantel-Haenszel fixed-effects or random-effects model. The I statistic was used to determine heterogeneity, whereas funnel plots and Egger's test were used to assess publication bias. In 15 clinical studies, 713 patients received RT combined with ICIs and 1,275 patients received only ICIs. With regard to PFS and OS, the hazard ratios of RT combined with ICIs were 0.79 (0.70, 0.89) and 0.72 (0.63, 0.82), respectively. In terms of ARR and ACR, the odds ratios (ORs) of RT combined with ICIs were 1.94 (1.19, 3.17) and 1.79 (1.08, 2.97), respectively. Subgroup analyses based on study type (RCT/NRCT), RT target (intracranial/extracranial), number of RT sites (single site), previous ICI resistance (yes/no), and sequencing of RT and ICIs (concurrent/post-RT ICIs) revealed that the addition of RT significantly prolonged PFS and OS. However, subgroup analyses based on radiation dose/fractionation indicated that the addition of hypofractionated RT significantly prolonged OS but not PFS. When grouped according to the level of PD-L1 expression, the addition of RT prolonged PFS only in patients who were PD-L1-negative. Furthermore, subgroup analyses of ARR and ACR signified that the combination therapy resulted in better local control of lesions outside the irradiation field in the hypofractionated RT, extracranial RT, and ICI-naïve subgroups. In terms of adverse events, the addition of RT did not significantly increase the adverse events rate but was associated with a higher pneumonia rate [OR values were 1.24 (0.92, 1.67) and 1.76 (1.12, 2.77), respectively]. Meta-analysis of existing data suggests that the addition of RT can significantly prolong PFS and OS in patients with metastatic NSCLC receiving ICIs. In addition to lesions in the irradiation field, RT can improve the local control rate of lesions outside the irradiation field immune activation. Combination therapy does not increase the overall risk of adverse reactions, except for pneumonia.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c6/9902364/9264aa8eebcf/fphar-14-1064227-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c6/9902364/d82ea4b3fee5/fphar-14-1064227-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c6/9902364/054d5322b916/fphar-14-1064227-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c6/9902364/174c3ffd5938/fphar-14-1064227-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c6/9902364/9264aa8eebcf/fphar-14-1064227-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c6/9902364/d82ea4b3fee5/fphar-14-1064227-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c6/9902364/054d5322b916/fphar-14-1064227-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c6/9902364/174c3ffd5938/fphar-14-1064227-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c6/9902364/9264aa8eebcf/fphar-14-1064227-g004.jpg

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引用本文的文献

[1]
Combinational therapeutic strategies to overcome resistance to immune checkpoint inhibitors.

Front Immunol. 2025-4-24

[2]
A Systematic Review of Pneumonitis Following Treatment with Immune Checkpoint Inhibitors and Radiotherapy.

Biomedicines. 2025-4-12

[3]
Effectiveness of radiotherapy in delaying treatment changes in primary or secondary immunorefractory oligoprogressive patients: preliminary results from a single-center study.

Discov Oncol. 2024-10-8

[4]
Immune checkpoint inhibitors with or without radiotherapy in metastatic non‑small cell lung cancer: A meta‑analysis and literature review.

Oncol Lett. 2024-8-9

[5]
Immune Checkpoint Inhibitors after Radiation Therapy Improve Overall Survival Rates in Patients with Stage IV Lung Cancer.

Cancers (Basel). 2023-8-25

本文引用的文献

[1]
Radiotherapy plus immune checkpoint blockade in PD(L)-1-resistant metastatic NSCLC.

Lancet Oncol. 2022-4

[2]
Radiotherapy plus immune checkpoint blockade in PD(L)-1-resistant metastatic NSCLC.

Lancet Oncol. 2022-4

[3]
Bone metastasis attenuates efficacy of immune checkpoint inhibitors and displays "cold" immune characteristics in Non-small cell lung cancer.

Lung Cancer. 2022-4

[4]
Brain metastases, patterns of intracranial progression, and the clinical value of upfront cranial radiotherapy in patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors.

Transl Lung Cancer Res. 2022-2

[5]
Pembrolizumab monotherapy or combination therapy for bone metastases in advanced non-small cell lung cancer: a real-world retrospective study.

Transl Lung Cancer Res. 2022-1

[6]
Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial.

Lancet Oncol. 2022-2

[7]
Association of Radiation Therapy With Risk of Adverse Events in Patients Receiving Immunotherapy: A Pooled Analysis of Trials in the US Food and Drug Administration Database.

JAMA Oncol. 2022-2-1

[8]
Systemic Immune Activation and Responses of Irradiation to Different Metastatic Sites Combined With Immunotherapy in Advanced Non-Small Cell Lung Cancer.

Front Immunol. 2021

[9]
Efficacy of single-site radiotherapy plus PD-1 inhibitors vs PD-1 inhibitors for oligometastatic non-small cell lung cancer.

J Cancer Res Clin Oncol. 2022-5

[10]
Immune Checkpoints Inhibitors and SRS/SBRT Synergy in Metastatic Non-Small-Cell Lung Cancer and Melanoma: A Systematic Review.

Int J Mol Sci. 2021-10-27

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