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Phase 2 or 3 results paper on KRAS in Colorectal cancer, in Journal of Clinical Oncology (2011), one of the most cited Europe PMC records with KRAS in its title.
Purpose: The addition of cetuximab to irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease. An updated survival analysis, including additional patients analyzed for tumor mutation status, was undertaken.
Patients and methods: Patients were randomly assigned to receive FOLFIRI with or without cetuximab. DNA was extracted from additional slide-mounted tumor samples previously used to assess epidermal growth factor receptor expression. Clinical outcome according to the tumor mutation status of KRAS and BRAF was assessed in the expanded patient series.
Results: The ascertainment rate of patients analyzed for tumor KRAS status was increased from 45% to 89%, with mutations detected in 37% of tumors. The addition of cetuximab to FOLFIRI in patients with KRAS wild-type disease resulted in significant improvements in overall survival (median, 23.5 v 20.0 months; hazard ratio [HR], 0.796; P =.0093), progression-free survival (median, 9.9 v 8.4 months; HR, 0.696; P =.0012), and response (rate 57.3% v 39.7%; odds ratio, 2.069; P <.001) compared with FOLFIRI alone. Significant interactions between KRAS status and treatment effect were noted for all key efficacy end points. KRAS mutation status was confirmed as a powerful predictive biomarker for the efficacy of cetuximab plus FOLFIRI. BRAF tumor mutation was a strong indicator of poor prognosis.
Conclusion: The addition of cetuximab to FOLFIRI as first-line therapy improves survival in patients with KRAS wild-type mCRC. BRAF tumor mutation is an indicator of poor prognosis.
Indexed on Europe PMC as PubMed record 21502544 (DOI 10.1200/jco.2010.33.5091). Its title names KRAS and its text names Colorectal cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea "Covalent chemistry for the RAS mutations that still have no drug" and no figure has been checked by an editor.
One of the most cited trial reports Europe PMC returns for KRAS in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
Shares Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer (CRYSTAL), Covalent chemistry for the RAS mutations that still have no drug, Off-the-shelf KRAS vaccines after pancreatic cancer surgery, Journal of Clinical Oncology.
Shares Covalent chemistry for the RAS mutations that still have no drug, Off-the-shelf KRAS vaccines after pancreatic cancer surgery, Journal of Clinical Oncology.
Shares Covalent chemistry for the RAS mutations that still have no drug, Colorectal cancer.
Shares Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer (CRYSTAL), Colorectal cancer.
Shares Covalent chemistry for the RAS mutations that still have no drug, Off-the-shelf KRAS vaccines after pancreatic cancer surgery.
Shares Covalent chemistry for the RAS mutations that still have no drug, Off-the-shelf KRAS vaccines after pancreatic cancer surgery.
Shares Covalent chemistry for the RAS mutations that still have no drug, Off-the-shelf KRAS vaccines after pancreatic cancer surgery.
Shares Covalent chemistry for the RAS mutations that still have no drug, Off-the-shelf KRAS vaccines after pancreatic cancer surgery, Colorectal cancer.