Trial reportJournal of the National Cancer Institute2024
Combining antivascular endothelial growth factor and anti-epidermal growth factor receptor antibodies: randomized phase II study of irinotecan and cetuximab with/without ramucirumab in second-line colorectal cancer (ECOG-ACRIN E7208).
Trial report in Journal of the National Cancer Institute, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01079780 (A Randomized Phase II Study of Irinotecan and Cetuximab With or Without the Anti-Angiogenic Antibody, Ramucirumab), which is not on this map. Cited by 6 papers.
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.
A Randomized Phase II Study of Irinotecan and Cetuximab With or Without the Anti-Angiogenic Antibody, Ramucirumab (IMC-1121B), in Advanced, K-ras Wild-Type Colorectal Cancer Following Progression on Bevacizumab-Containing Chemotherapy
Who cites it
6 citing papers in PubMed.
- Colorectal cancer pathogenesis, oncogenic signaling networks and targeted therapeutic advances.Molecular biomedicine · 2026Review
- Dual-mechanism of phytochemicals in cancer therapy: synergistic anti-angiogenic potency in cancer and proangiogenic impact against chemotherapy-induced cytotoxicity in vital organs.Frontiers in pharmacology · 2026Review
- Article
- Colorectal Cancer: Pathogenesis and Targeted Therapy.MedComm · 2025Review
- An overview of mechanisms, biomarkers, and treatment strategies for acquired anti-EGFR resistance in RAS wild-type colorectal cancer.Frontiers in pharmacology · 2025Review
- The role of PIK3CA gene mutations in colorectal cancer and the selection of treatment strategies.Frontiers in pharmacology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
backgroundEarly studies showed promise of combined anti-epidermal growth factor receptor (EGFR) plus anti-vascular endothelial growth factor (VEGF) antibodies for advanced colorectal cancer (CRC), yet this was later rejected as toxic and ineffective in studies not selected for RAS status. We studied advanced KRAS wild-type CRC, as second-line treatment, using irinotecan-cetuximab with or without the anti-VEGF receptor antibody ramucirumab.
methodsPatients with 1 prior regimen including fluoropyrimidine, oxaliplatin, and bevacizumab, with KRAS wild-type tumors were stratified by Eastern Cooperative Oncology Group Performance Score, time since last chemotherapy, and progression on oxaliplatin to irinotecan-cetuximab (IC) (180 mg/m2 and 500 mg/m2 every 2 weeks) vs modified ICR (irinotecan-cetuximab with ramucirumab 150 mg/m2 and 400 mg/m2 plus 6 mg/kg, respectively). A total of 102 patients were compared for progression-free survival (PFS) as primary endpoint (85% power for 70% improvement in median PFS from 4.5 to 7.65 months).
resultsOf the 102 enrolled, 44 treated with irinotecan-cetuximab and 45 with modified ramucirumab were evaluable. Median PFS was 6.0 months vs 9.2 months, respectively (hazard ratio = 0.75, P = .07; statistically significant by study design for P < .128). Response rate was 23% vs 36% (P = .27), and disease-control rate was 52% vs 73% (P = .05). Grade 3 or higher toxicity was equivalent. Overall survival was not significantly different at approximately 19 months.
conclusionPrevious phase 3 trials without RAS genotyping rejected combining anti-epidermal growth factor receptor and anti-VEGF drugs. In this randomized multicenter phase 2 study for KRAS wild-type CRC (all previously bevacizumab treated), the addition of ramucirumab to irinotecan and cetuximab improved PFS and disease control rate, showing the combination is feasible and effective. Further, phase 3 trials with appropriate patient-selection are required. (NCT01079780).
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