Evaluation of Immune Checkpoint Inhibitors for Colorectal Cancer: A Network Meta‑analysis

Overview

Journal Oncol Lett

Specialty Oncology

Date 2024 Oct 11

PMID 39390977

Authors

Chih-Chen Tzang

Yen-Wei Lee

Wei-Chen Lin

Long-Huei Lin

Yuan-Fu Kang

Ting-Yu Lin

Wei-Ting Wu

Ke-Vin Chang

Affiliations

Soon will be listed here.

Abstract

Colorectal cancer (CRC) is challenging to treat due to its high metastatic rate. Recent strategies have focused on combining immune checkpoint inhibitors (ICIs) with other treatments. The aim of the present study was to conduct a network meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and adverse effects of different ICI treatments for CRC. A literature search for RCTs was conducted using PubMed, the Cochrane Library, Embase, ClinicalTrials.gov and Web of Science databases, covering the period from the inception of each database until April 2024. A total of 12 RCTs involving 2,050 participants were selected for inclusion in the analysis. The network meta-analysis employed the MetaInsight tool to assess multiple endpoints. The criteria for study selection were based on the Population, Intervention, Comparison, Outcome and Studies framework as follows: i) Population, patients with CRC; ii) intervention, studies using ICI to treat CRC; iii) comparison, active comparators, including placebo; iv) outcome, overall survival, progression-free survival, objective response rate and adverse events; and v) study design, RCTs. The results of the analysis revealed that programmed cell death-ligand 1 (PD-L1) inhibitors significantly improved overall survival time [mean difference (MD), 2.28 months; 95% confidence interval (CI), 0.44 to 4.11], while programmed cell death protein 1 (PD-1) inhibitors exhibited a superior progression-free survival time (MD, 4.79 months; 95% CI, 3.18 to 6.40) compared with active comparators. However, none of the ICI treatments had significant differences in odds ratios for the objective response rate and adverse events compared with active comparators. These findings indicate that treatment with PD-L1 and PD-1 inhibitors improved the overall survival time and delayed disease progression in patients with CRC. These findings offer valuable insights for future research aimed at improving CRC patient outcomes.

References

Antoniotti C, Rossini D, Pietrantonio F, Catteau A, Salvatore L, Lonardi S . Upfront FOLFOXIRI plus bevacizumab with or without atezolizumab in the treatment of patients with metastatic colorectal cancer (AtezoTRIBE): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2022; 23(7):876-887. DOI: 10.1016/S1470-2045(22)00274-1. View

Tabernero J, Grothey A, Arnold D, de Gramont A, Ducreux M, ODwyer P . MODUL cohort 2: an adaptable, randomized, signal-seeking trial of fluoropyrimidine plus bevacizumab with or without atezolizumab maintenance therapy for BRAF metastatic colorectal cancer. ESMO Open. 2022; 7(5):100559. PMC: 9588902. DOI: 10.1016/j.esmoop.2022.100559. View

Andre T, Shiu K, Kim T, Jensen B, Jensen L, Punt C . Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020; 383(23):2207-2218. DOI: 10.1056/NEJMoa2017699. View

Buchbinder E, Desai A . CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition. Am J Clin Oncol. 2015; 39(1):98-106. PMC: 4892769. DOI: 10.1097/COC.0000000000000239. View

Zeng T, Fang X, Lu J, Zhong Y, Lin X, Lin Z . Efficacy and safety of immune checkpoint inhibitors in colorectal cancer: a systematic review and meta-analysis. Int J Colorectal Dis. 2021; 37(1):251-258. PMC: 8760220. DOI: 10.1007/s00384-021-04028-z. View

Jove M, Vilarino N, Nadal E . Impact of baseline steroids on efficacy of programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) blockade in patients with advanced non-small cell lung cancer. Transl Lung Cancer Res. 2020; 8(Suppl 4):S364-S368. PMC: 6987359. DOI: 10.21037/tlcr.2019.06.06. View

Sterne J, Savovic J, Page M, Elbers R, Blencowe N, Boutron I . RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019; 366:l4898. DOI: 10.1136/bmj.l4898. View

Hossain M, Karuniawati H, Jairoun A, Urbi Z, Ooi D, John A . Colorectal Cancer: A Review of Carcinogenesis, Global Epidemiology, Current Challenges, Risk Factors, Preventive and Treatment Strategies. Cancers (Basel). 2022; 14(7). PMC: 8996939. DOI: 10.3390/cancers14071732. View

Byron Y, Yegorova-Lee S, Tio M . Do corticosteroids affect immunotherapy efficacy in malignancy? - A systematic review. Cancer Med. 2024; 13(18):e70254. PMC: 11420628. DOI: 10.1002/cam4.70254. View

10.

Carbone D, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M . First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 376(25):2415-2426. PMC: 6487310. DOI: 10.1056/NEJMoa1613493. View

11.

Ducreux M, Tabernero J, Grothey A, Arnold D, ODwyer P, Gilberg F . Clinical and exploratory biomarker findings from the MODUL trial (Cohorts 1, 3 and 4) of biomarker-driven maintenance therapy for metastatic colorectal cancer. Eur J Cancer. 2023; 184:137-150. DOI: 10.1016/j.ejca.2023.01.023. View

12.

Meltzer S, Negard A, Bakke K, Hamre H, Kersten C, Hofsli E . Early radiologic signal of responsiveness to immune checkpoint blockade in microsatellite-stable/mismatch repair-proficient metastatic colorectal cancer. Br J Cancer. 2022; 127(12):2227-2233. PMC: 9726864. DOI: 10.1038/s41416-022-02004-0. View

13.

Shan T, Chen S, Wu T, Yang Y, Li S, Chen X . PD-L1 expression in colon cancer and its relationship with clinical prognosis. Int J Clin Exp Pathol. 2020; 12(5):1764-1769. PMC: 6947132. View

14.

Biller L, Schrag D . Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA. 2021; 325(7):669-685. DOI: 10.1001/jama.2021.0106. View

15.

Chen E, Jonker D, Loree J, Kennecke H, Berry S, Couture F . Effect of Combined Immune Checkpoint Inhibition vs Best Supportive Care Alone in Patients With Advanced Colorectal Cancer: The Canadian Cancer Trials Group CO.26 Study. JAMA Oncol. 2020; 6(6):831-838. PMC: 7206536. DOI: 10.1001/jamaoncol.2020.0910. View

16.

Duffy A, Ulahannan S, Makorova-Rusher O, Rahma O, Wedemeyer H, Pratt D . Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol. 2016; 66(3):545-551. PMC: 5316490. DOI: 10.1016/j.jhep.2016.10.029. View

17.

Lyu N, Kong Y, Li X, Mu L, Deng H, Chen H . Ablation Reboots the Response in Advanced Hepatocellular Carcinoma With Stable or Atypical Response During PD-1 Therapy: A Proof-of-Concept Study. Front Oncol. 2020; 10:580241. PMC: 7581675. DOI: 10.3389/fonc.2020.580241. View

18.

Tokunaga A, Sugiyama D, Maeda Y, Betof Warner A, Panageas K, Ito S . Selective inhibition of low-affinity memory CD8 T cells by corticosteroids. J Exp Med. 2019; 216(12):2701-2713. PMC: 6888983. DOI: 10.1084/jem.20190738. View

19.

Owen R, Bradbury N, Xin Y, Cooper N, Sutton A . MetaInsight: An interactive web-based tool for analyzing, interrogating, and visualizing network meta-analyses using R-shiny and netmeta. Res Synth Methods. 2019; 10(4):569-581. PMC: 6973101. DOI: 10.1002/jrsm.1373. View

20.

Mettu N, Ou F, Zemla T, Halfdanarson T, Lenz H, Breakstone R . Assessment of Capecitabine and Bevacizumab With or Without Atezolizumab for the Treatment of Refractory Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA Netw Open. 2022; 5(2):e2149040. PMC: 8857687. DOI: 10.1001/jamanetworkopen.2021.49040. View