Trial reportInternational journal of cancer2016
A randomized, placebo-controlled, phase 1/2 study of tivantinib (ARQ 197) in combination with irinotecan and cetuximab in patients with metastatic colorectal cancer with wild-type KRAS who have received first-line systemic therapy.
Trial report in International journal of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 3 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- Second-line systemic treatment for metastatic colorectal cancer: A systematic review and Bayesian network meta-analysis based on RCT.PloS one · 2024Pooled it
- Incidence and risk of fatigue in cancer patients treated with MET inhibitors: A systematic review and meta-analysis.Medicine · 2019Pooled it
- The role of biological therapy in metastatic colorectal cancer after first-line treatment: a meta-analysis of randomised trials.British journal of cancer · 2014Pooled it
- Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib.Oncotarget · 2016Trial
- Research progress of small molecule protein kinase inhibitors (SMKIs) in the treatment of colorectal cancer: mechanism, application, and future prospects.Frontiers in pharmacology · 2026Review
- Case Report: Remarkable response to savolitinib plus chemotherapy and bevacizumab in second-line treatment of MET amplified colon cancer with liver metastasis.Frontiers in oncology · 2026Article
- Targeting mesenchymal-epithelial transition factor signaling in cancer: from genetic alterations to clinical advances and future prospects.Molecular biology reports · 2025Review
- Evolving roles of MET as a therapeutic target in NSCLC and beyond.Nature reviews. Clinical oncology · 2025Review
- Anti-EGFR Therapy in Metastatic Colorectal Cancer: Identifying, Tracking, and Overcoming Resistance.Cancers · 2025Review
- Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors.International journal of molecular sciences · 2023Review
- Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond.World journal of gastroenterology · 2023Review
- Resistance to targeted therapy in metastatic colorectal cancer: Current status and new developments.World journal of gastroenterology · 2023Review
- Deciphering treatment resistance in metastatic colorectal cancer: roles of drug transports, EGFR mutations, and HGF/c-MET signaling.Frontiers in pharmacology · 2023Review
- Review
- Article
- Therapeutic Strategies for Ovarian Cancer in Point of HGF/c-MET Targeting.Medicina (Kaunas, Lithuania) · 2022Review
- Opportunities and challenges of targeting c-Met in the treatment of digestive tumors.Frontiers in oncology · 2022Review
- Epidermal Growth Factor Receptor Inhibitor Treatment Timing does not Impact Survival in Stage 4 Colon Cancer Treatment: A Retrospective Study.Kansas journal of medicine · 2022Article
- Emerging actionable targets to treat therapy-resistant colorectal cancers.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Personalizing first-line treatment in advanced colorectal cancer: Present status and future perspectives.Journal of clinical and translational research · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 15 institutions in 4 countries.
Funding
Abstract
Cetuximab in combination with an irinotecan-containing regimen is a standard treatment in patients with KRAS wild-type (KRAS WT), metastatic colorectal cancer (mCRC). We investigated the addition of the oral MET inhibitor tivantinib to cetuximab + irinotecan (CETIRI) based on preclinical evidence that activation of the MET pathway may confer resistance to anti-EGFR therapy. Previously treated patients with KRAS WT advanced or mCRC were enrolled. The phase 1, open-label 3 + 3, dose-escalation study evaluated the safety and maximally tolerated dose of tivantinib plus CETIRI. The phase 2, randomized, double-blinded, placebo-controlled study of biweekly CETIRI plus tivantinib or placebo was restricted to patients who had received only one prior line of chemotherapy. The phase 2 primary endpoint was progression-free survival (PFS). The recommended phase 2 dose was tivantinib (360 mg/m(2) twice daily) with biweekly cetuximab (500 mg/m(2)) and irinotecan (180 mg/m(2)). Among 117 patients evaluable for phase 2 analysis, no statistically significant PFS difference was observed: 8.3 months on tivantinib vs. 7.3 months on placebo (HR, 0.85; 95% confidence interval, 0.55-1.33; P = 0.38). Subgroup analyses trended in favor of tivantinib in patients with MET-High tumors by immunohistochemistry, PTEN-Low tumors, or those pretreated with oxaliplatin, but subgroups were too small to draw conclusions. Neutropenia, diarrhea, nausea and rash were the most frequent severe adverse events in tivantinib-treated patients. The combination of tivantinib and CETIRI was well tolerated but did not significantly improve PFS in previously treated KRAS WT mCRC. Tivantinib may be more active in specific subgroups.
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What OpenQuestion holds
Registered trials
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.