Marta Schirripa1, Floriana Nappo2, Chiara Cremolini3, Lisa Salvatore4, Daniele Rossini3, Maria Bensi4, Gianluca Businello5, Filippo Pietrantonio6, Giovanni Randon7, Giovanni Fucà7, Alessandra Boccaccino3, Francesca Bergamo1, Sara Lonardi1, Angelo Paolo Dei Tos8, Matteo Fassan8, Fotios Loupakis9. 1. Department of Oncology, Veneto Institute of Oncology IOV IRCCS, Padua, Italy. 2. Department of Oncology, Veneto Institute of Oncology IOV IRCCS, Padua, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy. 3. Unit of Medical Oncology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. 4. Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy. 5. Unit of Surgical Pathology, Department of Medicine (DIMED), University of Padua, Padua, Italy. 6. Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 7. Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy. 8. Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy. 9. Department of Oncology, Veneto Institute of Oncology IOV IRCCS, Padua, Italy. Electronic address: fotiosloupakis@gmail.com.
Abstract
BACKGROUND: Kirsten rat sarcoma viral oncogene (KRAS) G12C mutation occurs in about 4% of colorectal cancers (CRCs). Recently, KRAS G12C was identified to be a potential drug target and predictor of response to the novel on AMG510 target treatment. We described the clinicopathologic features and prognosis of KRAS G12C-mutated metastatic CRCs compared to other KRAS mutation. PATIENTS AND METHODS: Clinicopathologic features and outcome data of KRAS-mutated metastatic CRC (mCRC) patients referred to 3 Italian oncology units from January 2010 to December 2018 were collected. A cohort of KRAS-mutant mCRC patients referred to the Department of Medical Oncology at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy) within the same time frame was included as external validation. RESULTS: A total of 839 KRAS-mutated mCRC cases were included in the main patient population. A total of 145 patients (17%) had KRAS G12C mutation. Our analyses showed that patients harboring KRAS G12C mutation were more likely to be men and to present lung and liver metastases, and were less likely to have peritoneal spread. KRAS G12C mutation was associated with shorter overall survival compared to other KRAS mutations (hazard ratio, 1.32; 95% confidence interval, 1.07-1.63; P = .009). Such results were confirmed in the external validation cohort. CONCLUSION: The knowledge of the distinctive traits of KRAS G12C-mutated CRC patients is crucial to future translational research studies, clinical trial design, and proper interpretation of results.
BACKGROUND: Kirsten rat sarcoma viral oncogene (KRAS) G12C mutation occurs in about 4% of colorectal cancers (CRCs). Recently, KRASG12C was identified to be a potential drug target and predictor of response to the novel on AMG510 target treatment. We described the clinicopathologic features and prognosis of KRASG12C-mutated metastatic CRCs compared to other KRAS mutation. PATIENTS AND METHODS: Clinicopathologic features and outcome data of KRAS-mutated metastatic CRC (mCRC) patients referred to 3 Italian oncology units from January 2010 to December 2018 were collected. A cohort of KRAS-mutant mCRC patients referred to the Department of Medical Oncology at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy) within the same time frame was included as external validation. RESULTS: A total of 839 KRAS-mutated mCRC cases were included in the main patient population. A total of 145 patients (17%) had KRASG12C mutation. Our analyses showed that patients harboring KRASG12C mutation were more likely to be men and to present lung and liver metastases, and were less likely to have peritoneal spread. KRASG12C mutation was associated with shorter overall survival compared to other KRAS mutations (hazard ratio, 1.32; 95% confidence interval, 1.07-1.63; P = .009). Such results were confirmed in the external validation cohort. CONCLUSION: The knowledge of the distinctive traits of KRASG12C-mutated CRCpatients is crucial to future translational research studies, clinical trial design, and proper interpretation of results.
Authors: Meredith Li; Faeze Keshavarz-Rahaghi; Gale Ladua; Lucas Swanson; Caroline Speers; Daniel J Renouf; Howard J Lim; Janine M Davies; Sharlene Gill; Heather C Stuart; Stephen Yip; Jonathan M Loree Journal: Ther Adv Med Oncol Date: 2022-06-06 Impact factor: 5.485
Authors: Jason T Henry; Oluwadara Coker; Saikat Chowdhury; John Paul Shen; Van K Morris; Arvind Dasari; Kanwal Raghav; Maliha Nusrat; Bryan Kee; Christine Parseghian; Shubham Pant; Nikeshan Jeyakumar; Limin Zhu; Yujiro Nishioka; David Fogelman; Robert A Wolff; David Hong; Michael J Overman; JeanNicolas Vauthey; Scott Kopetz; Benny Johnson Journal: JCO Precis Oncol Date: 2021-04-06