Trial reportJAMA oncology2025
First-Line Systemic Treatment for Initially Unresectable Colorectal Liver Metastases: Post Hoc Analysis of the CAIRO5 Randomized Clinical Trial.
Trial report in JAMA oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Treatment Strategies in Colorectal Cancer Patients With Initially Unresectable Liver-only Metastases CAIRO5 a Randomized Phase 3 Study of the Dutch Colorectal Cancer Group (DCCG)
Development of a cfDNA 5mC/5hmC-based Epigenetic Biomarker Panel to Predict Chemotherapy Efficacy in Metastatic Colorectal Cancer
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Triplet chemotherapy combined with anti Epidermal Growth Factor Receptor treatment in RAS wild-type colorectal cancer: a network metanalysis.The oncologist · 2026Pooled it
- Trial
- Trial
- Integrated Evaluation of Survival, Surgical Conversion, and Toxicity for Induction Therapy in Initially Unresectable Colorectal Liver Metastases: An Individual Patient Data Network Meta-analysis.Annals of surgical oncology · 2026Article
- Large-scale AI-guided liver malignancy diagnosis: multicenter study and a single-arm trial.Nature medicine · 2026Article
- Development and validation of a multivariable CT-based Delta-radiomics model for predicting efficacy to bevacizumab therapy in patients with colorectal liver metastases.Translational cancer research · 2026Article
- Article
- Exploring the Upper Limit: The Added Value of Local Treatment in Patients with Multiple Colorectal Liver Metastases: An Amsterdam Colorectal Liver Met Registry (AmCORE)-Based Study.Cardiovascular and interventional radiology · 2026Article
- Engineered TIGIT-Blockade Membrane Vesicles Synergize with Microwave Ablation to Mediate Liver Metastases Eradication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Preclinical Models of Colorectal Cancer Liver Metastasis: Therapeutic Evaluation and Translational Implications.Oncology research · 2026Review
- Comparative study of triple intravenous chemotherapy versus dual chemotherapy combined with hepatic arterial infusion in patients with liver metastases from colorectal cancer.Frontiers in oncology · 2026Article
- Laparoscopic resection combined with ablation for multiple colorectal liver metastases: a multicentre propensity-matched analysis.Surgical endoscopy · 2025Article
- The surgical perspective on CAIRO5 and beyond: all patients with colorectal liver metastases should be evaluated by a liver surgeon, but what defines resectability?Journal of gastrointestinal oncology · 2025Article
- Rethinking surrogate endpoints in metastatic colorectal cancer: counting chickens only when they hatch.Journal of gastrointestinal oncology · 2025Article
- Comparative effects of oxaliplatin-based versus irinotecan-based regimens combined with capecitabine and bevacizumab in patients with colorectal cancer and liver metastases.American journal of cancer research · 2025Article
- Errors in Figures 2 and 3.JAMA oncology · 2025Article
Corrections and comments
- Commented on by
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- Erratum issued
Authors and funding
32 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Importance: In patients with colorectal cancer and unresectable liver-only metastases (CRLM), treatment with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) plus irinotecan (FOLFOXIRI) and bevacizumab vs FOLFOX/folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus bevacizumab increased progression-free survival, response, and R0/R1 resection/ablation rates, as well as toxic effects in RAS/BRAFV600E-variant and/or right-sided tumors. FOLFOX/FOLFIRI-panitumumab vs FOLFOX/FOLFIRI-bevacizumab increased response at the cost of more toxic effects in RAS/BRAFV600E wild-type, left-sided tumors. Objective: To present long-term outcomes of treatment with FOLFOXIRI plus bevacizumab vs FOLFOX/FOLFIRI plus bevacizumab and FOLFOX/FOLFIRI plus panitumumab vs FOLFOX/FOLFIRI + bevacizumab. Design, Setting, and Participants: The randomized phase 3 CAIRO5 trial included patients with initially unresectable CRLM in 46 Dutch centers and 1 Belgian center between November 2014 and January 2022. A liver expert panel repeatedly evaluated resectability. Intervention: Patients with RAS/BRAFV600E-variant and/or right-sided tumors randomly received FOLFOX/FOLFIRI-bevacizumab (group 1) or FOLFOXIRI-bevacizumab (group 2), and those with RAS/BRAFV600E wild-type, left-sided tumors received FOLFOX/FOLFIRI-bevacizumab (group 3) or FOLFOX/FOLFIRI-panitumumab (group 4). Adjuvant chemotherapy (ACT) after complete local treatment was recommended but not standard. Main Outcomes and Measures: Overall survival (OS) was analyzed as a secondary outcome. Other outcomes were post hoc analyses. Results: A total of 530 patients (327 male [62%] and 203 female individuals [38%]; median age, 62 [IQR, 54-69] years) were randomized: 148 in group 1, 146 in group 2, 118 in group 3, and 118 in group 4. The median OS in group 1 was 23.6 (95% CI, 20.1-27.5) vs 24.1 (95% CI, 21.0-30.9) months in group 2 (hazard ratio [HR], 0.90; 95% CI, 0.70-1.17; P = .44), and 39.9 (95% CI, 30.7-44.6) in group 3 vs 38.3 (95% CI, 35.3-51.3) months in group 4 (HR, 0.95; 95% CI, 0.68-1.32; P = .75). OS was longest after complete local treatment without early (≤6 months) recurrence (64.3 months; 95% CI, 57.6 to not reached) and salvage local treatment options after early recurrence (58.9; 95% CI, 47.3 to not reached), followed by patients without salvage local treatment after early recurrence (30.5; 95% CI, 24.4-33.4) and with incomplete local treatment (28.7; 95% CI, 25.9-38.3), and worst in patients with continued unresectability (18.3; 95% CI, 15.7-20.0). After confounder adjustment, ACT was associated with longer OS (HR, 0.66; 95% CI, 0.44-0.98) and relapse-free survival (HR, 0.65; 95% CI, 0.48-0.88) and less early recurrence without salvage local treatment (odds ratio, 0.46; 95% CI, 0.25-0.85). Conclusions and Relevance: These results support using FOLFOX/FOLFIRI-bevacizumab for patients with initially unresectable CRLM irrespective of RAS/BRAFV600E status and tumor sidedness. Patients with complete local liver treatment with salvage local treatment in case of early recurrence had the longest OS. ACT might be considered for these patients. Trial Registration: ClinicalTrials.gov NCT02162563.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.