The Addition of Concurrent Immune Checkpoint Inhibitors for Chemoradiotherapy With Consolidative Immune Checkpoint Inhibitors in Unresectable Cancers - A Systematic Review and Meta-Analysis

Sep 23, 2026

A systematic review and meta-analysis evaluates whether adding concurrent immune checkpoint inhibitors (ICIs) to chemoradiotherapy (CRT) followed by consolidative ICIs improves outcomes in unresectable cancers. PubMed, Embase, and Cochrane Library searches identified RCTs comparing CRT plus consolidative ICIs versus CRT alone, and CRT with both concurrent and consolidative ICIs versus CRT alone. Primary endpoints were overall survival and progression-free survival. Thirteen RCTs (6868 patients) and 14 cohort studies (4724) were included, with mirror-design network meta-analysis used to reduce bias. Results show concurrent addition did not enhance OS or PFS and may attenuate CRT plus consolidative ICI benefits, guiding future RCT design.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Abstract

Introduction

Keywords and study background

Outcomes and evidence synthesis

Methods and analysis

Literature search and eligibility

Outcomes and bias reduction

Results and conclusions

Efficacy signals for OS and PFS

Impact of adding concurrent ICIs

Abbreviations

International Journal of Cancer RESEARCH ARTICLE OPEN ACCESS Cancer Therapy and Prevention The Addition of Concurrent Immune Checkpoint Inhibitors for Chemoradiotherapy With Consolidative Immune Checkpoint Inhibitors in Unresectable Cancers: A Systematic Review and Meta-Analysis Xu Tong1 | Zhenting Liu2 | Xiaoxiang Zhou2 | Nan Bi1 | Yibo Gao3,4,5,6 1Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China | 2Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China | 3Central Laboratory & Shenzhen Key Laboratory of Epigenetics and Precision Medicine for Cancers, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China | 4State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China | 5Laboratory of Translational Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China | 6Department of Gastroenterology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancers Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China Correspondence: Nan Bi ([binan@cicams.ac.cn](binan@cicams.ac.cn)) | Yibo Gao ([gaoyibo@cicams.ac.cn](gaoyibo@cicams.ac.cn)) Received: 16 January 2026 | Revised: 28 April 2026 | Accepted: 29 April 2026 Keywords: chemoradiotherapy | concurrent versus consolidative | immune checkpoint inhibitors | locally advanced cancers ABSTRACT Following the success of chemoradiotherapy (CRT) combined with consolidative immune checkpoint inhibitors (ICIs) in locally advanced tumors, over 30 ongoing randomized controlled trials (RCTs) are investigating the potential benefits of adding concurrent ICIs. To investigate the differences in efficacy and safety between adding and not adding concurrent ICIs to CRT followed by consolidative ICIs, a literature search was conducted in PubMed, Embase, and the Cochrane Library, incorporating RCTs comparing CRT combined with consolidative ICIs versus CRT alone, or CRT with both concurrent and consolidative ICIs versus CRT alone. The primary outcomes were overall survival (OS) and progression-free survival (PFS). To reduce potential bias, an additional mirror-design analysis was performed through network meta-analysis. A total of 13 RCTs comprising 6868 patients and 14 cohort studies comprising 4724 patients were included. While patients treated with CRT and consolidative ICIs demonstrated significantly superior OS and PFS to patients treated with CRT alone in RCTs (HR of OS, 0.743, 95% CI, 0.654–0.843; HR | Abbreviations: AE, adverse events; ATE, atezolizumab; AVE, avelumab; CAM, camrelizumab; CC, cervical cancer; cCRT, concurrent chemoradiotherapy; CI, confidence interval; CRT, chemoradiotherapy; CTCAE, common terminology criteria for adverse events; CTLA-4, cytotoxic T lymphocyte-associated protein 4; DUR, durvalumab; ESCC, esophageal squamous cell carcinoma; FDA, Food and Drug Administration; HNSCC, head and neck squamous cell carcinoma; HR, hazard ratio; ICIs, immune checkpoint inhibitors; IPI, ipilimumab; irAEs, immune-related adverse events; LS-SCLC, limited-stage small cell lung cancer; NCCN, National Comprehensive Cancer Network; NIV, nivolumab; NPC, nasopharyngeal carcinoma; NR, not reached; NSCLC, nonsmall-cell lung cancer; OR, odds ratio; ORR, objective response rate; OS, overall survival; PBO, pla

FAQs

What question does this review address about concurrent immune checkpoint inhibitors?

It assesses whether adding concurrent ICIs to CRT (followed by consolidative ICIs) improves efficacy and safety compared with CRT followed by consolidative ICIs alone.

How were studies selected and what databases were searched?

The review searched PubMed, Embase, and the Cochrane Library, including RCTs that compared CRT plus consolidative ICIs versus CRT alone, and CRT with both concurrent and consolidative ICIs versus CRT alone.

What were the primary outcomes analyzed in the meta-analysis?

Overall survival (OS) and progression-free survival (PFS) were the primary outcomes, with additional mirror-design analysis via network meta-analysis to reduce potential bias.

Sep 23, 2026

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