Academic Journal
Prospective Biomarker Study in Advanced RAS Wild-Type Colorectal Cancer: POSIBA Trial (GEMCAD 10-02)
| العنوان: | Prospective Biomarker Study in Advanced RAS Wild-Type Colorectal Cancer: POSIBA Trial (GEMCAD 10-02) |
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| المؤلفون: | García-Albéniz, Xabier, Alonso, Vicente, Escudero, Pilar, Méndez, Miguel, Gallego, Javier, Rodríguez, Jose Ramon, Salud, Antonia, Fernández-Plana, Julen, Manzano, Hermini, Zanui, Montserrat, Falcó, Ester, Feliu, Jaime, Gil, Mireia, Fernández-Martos, Carlos, Bohn, Uriel, Alonso, Carmen, Calderero, Verónica, Rojo, Federico, Cuatrecasas, Miriam, Maurel, Joan |
| المصدر: | The Oncologist ; volume 24, issue 11, page e1115-e1122 ; ISSN 1083-7159 1549-490X |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2019 |
| الوصف: | Background RAS testing is used to select patients with anti-epidermal growth factor receptor (EGFR) therapies sensitivity in metastatic colorectal cancer (mCRC). However, other biomarkers such as BRAF, PIK3CA/PTEN, and p-IGF-1R+/MMP7+ (double positive [DP] phenotype) have not been prospectively assessed to predict anti-EGFR resistance. Materials and Methods We designed a multicenter prospective trial (NCT01276379) to evaluate whether the biomarkers BRAF mutation, PIK3CA mutation/PTEN loss, and DP phenotype can improve the prediction for 12-months progression-free survival (PFS) over the use of clinical variables exclusively in patients with RAS wild-type (WT) mCRC treated with standard chemotherapy plus biweekly cetuximab as first-line therapy. The planned sample size was 170 RAS WT patients to detect a 20% difference in 12-month PFS based on the analysis of clinical and selected biomarkers (α = .05, β = .2). The discriminatory capacity of the biomarkers was evaluated using receiver operating characteristic curves. Results We included 181 RAS WT patients. The biomarker distribution was as follows: BRAF mutant, 20 patients (11%); PIK3CA mutated/PTEN loss, 98 patients (58%); DP, 23 patients (12.7%). The clinical variables in the clinical score were progression status >0, left-sided tumor, and resectable liver metastasis as the only metastatic site. The area under the curve (AUC) of the score containing the clinical variables was 0.67 (95% confidence interval [CI], 0.60–0.75). The AUC of the score with clinical variables and BRAF mutational status was 0.68 (0.61–0.75, p = .37). The AUC of the score with clinical variables and PI3KCA mutation/PTEN status was 0.69 (0.61–0.76, p = .32). The AUC of the score with clinical variables and DP phenotype was 0.66 (0.58–0.73, p = .09). Conclusion The addition of BRAF, PIK3CA/PTEN, and DP to a clinical score does not improve the discrimination of 12-month PFS. Implications for Practice This prospective biomarker design study has important clinical implications ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1634/theoncologist.2018-0728 |
| الاتاحة: | http://dx.doi.org/10.1634/theoncologist.2018-0728 https://onlinelibrary.wiley.com/doi/pdf/10.1634/theoncologist.2018-0728 https://onlinelibrary.wiley.com/doi/full-xml/10.1634/theoncologist.2018-0728 https://academic.oup.com/oncolo/article-pdf/24/11/e1115/41918016/oncolo_24_11_e1115.pdf |
| Rights: | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| رقم الانضمام: | edsbas.9CEC1435 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1634/theoncologist.2018-0728 |
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