Trial reportInvestigational new drugs2015
Safety and efficacy of the addition of simvastatin to cetuximab in previously treated KRAS mutant metastatic colorectal cancer patients.
Trial report in Investigational new drugs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis 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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy.British journal of cancer · 2017Pooled it
- Lipid metabolism as a central driver of immune remodeling and therapeutic vulnerability in metastatic colorectal cancer.Lipids in health and disease · 2026Review
- Squalene synthase induces ERα expression via cholesterol supplementation to confer statin resistance in lung cancer cells.Cancer cell international · 2026Article
- Review
- Statins in the context of precision cancer medicine: important factors to consider.Medical oncology (Northwood, London, England) · 2025Review
- The Mevalonate Pathway in the Radiation Response of Cancer.International journal of radiation oncology, biology, physics · 2025Review
- Review
- Statins as anti-tumor agents: A paradigm for repurposed drugs.Cancer reports (Hoboken, N.J.) · 2024Review
- Review
- Role of non-canonical post-translational modifications in gastrointestinal tumors.Cancer cell international · 2023Review
- Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance.Antibiotics (Basel, Switzerland) · 2023Review
- Statin as a therapeutic agent in gastroenterological cancer.World journal of gastrointestinal oncology · 2022Review
- Simvastatin in the Treatment of Colorectal Cancer: A Review.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- Review
- Strategies to tackle RAS-mutated metastatic colorectal cancer.ESMO open · 2021Review
- Statin as a Potential Chemotherapeutic Agent: Current Updates as a Monotherapy, Combination Therapy, and Treatment for Anti-Cancer Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The Heterogeneity of Lipid Metabolism in Cancer.Advances in experimental medicine and biology · 2021Article
- Lipid Metabolism Regulates Oxidative Stress and Ferroptosis in RAS-Driven Cancers: A Perspective on Cancer Progression and Therapy.Frontiers in molecular biosciences · 2021Review
- MEK nuclear localization promotes YAP stability via sequestering β-TrCP in KRAS mutant cancer cells.Cell death and differentiation · 2019Article
- Drug repurposing to overcome resistance to various therapies for colorectal cancer.Cellular and molecular life sciences : CMLS · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCetuximab is registered for use in colorectal cancer (CRC) patients with RAS wild-type tumours only. Simvastatin blocks the mevalonate pathway and thereby interferes with the post-translational modification (prenylation) of KRAS. We hypothesize that the activated KRAS pathway in KRAS mutant tumors can be inhibited by simvastatin rendering these tumors sensitive to the EGFR inhibitor cetuximab.
methodsA Simon two-stage, single-arm, phase II study was performed to test the efficacy and safety of the addition of simvastatin to cetuximab in patients with a KRAS mutation in their CRC tumour who were previously treated with fluoropyrimidine, oxaliplatin and irinotecan based regimens. The primary endpoint was to test the percentage of patients alive and free from progression 12.5 weeks after the first administration of cetuximab. Our hypothesis was that at least 40% was free from progression, comparable to, though slightly lower than in KRAS wild-type patients.
resultsFour of 18 included patients (22.2%) were free from progression at the primary endpoint time. The time to progression in these 4 patients ranged from 20.3 to 47 weeks.
conclusionBased on the current study we conclude that the theoretical concept of KRAS modulation with simvastatin was not applicable in the clinic, as we were not able to restore sensitivity to cetuximab in CRC patients harbouring a somatic KRAS mutation.
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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.