Prognostic and predictive biomarkers in metastatic colorectal cancer anti-EGFR therapy

Nigro, Cristiana Lo; Ricci, Vincenzo; Vivenza, Daniela; Granetto, Cristina; Fabozzi, Teresa; Miraglio, Emanuela; Merlano, Marco

doi:10.3748/wjg.v22.i30.6944

Cited by 60 publications

(52 citation statements)

References 66 publications

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“…Sin embargo, la mutación en el NRAS predice resistencia a los tratamientos con mAbs-EGFR en el cáncer colorrectal metastásico 47 . De otro lado, el impacto pronóstico del estado de BRAF sigue siendo controvertido 102,103 . Sin embargo, las investigaciones continúan para lograr afinar la utilidad clínica de estos biomarcadores [47][48][49]104 , ya que los estudios existentes han demostrado que entre los pacientes con cáncer colorrectal avanzado con el gen KRAS en estado nativo y que albergan mutaciones en los genes de NRAS, BRAF, PIK3CA, o PTEN, se puede demostrar resistencia al tratamiento con mAbs-EGFR 105 .…”

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¿Existen ventajas clínicas al evaluar el estado de los genes KRAS, NRAS, BRAF, PIK3CA, PTEN y HER2 en pacientes con cáncer colorrectal?

2017

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Section: Referenciasunclassified

¿Existen ventajas clínicas al evaluar el estado de los genes KRAS, NRAS, BRAF, PIK3CA, PTEN y HER2 en pacientes con cáncer colorrectal?

2017

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“…3,4 Cetuximab and panitumumab are two EGFR antibodies that have been shown to improve overall survival in mCRC patients. 3,4 Cetuximab and panitumumab are two EGFR antibodies that have been shown to improve overall survival in mCRC patients.…”

Section: Introductionmentioning

confidence: 99%

Molecular testing in metastatic colorectal adenocarcinoma cytology cell pellets

McHugh

Dermawan

Cheng

et al. 2019

Diagnostic Cytopathology

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Background: Mutational status for KRAS, NRAS, and BRAF genes should be performed on all colorectal carcinoma (CRC) specimens in order to guide targeted therapy selection for metastatic disease. Mutations are typically assessed via polymerase chain reaction and/or next generation sequencing (NGS) on formalin-fixed paraffinembedded tissues. With minimally invasive diagnostic methodologies, the cytology cell pellet obtained by fine-needle aspiration (FNA) can serve as an alternative source of tumor deoxyribonucleic acid. Methods: An electronic record review of the cytopathology files (CoPathPlus, Cerner Corp., North Kansas City, Missouri) from September 1, 2015 through December 31, 2018 was conducted. All cytology specimens obtained via FNA and diagnosed as metastatic CRC on which NGS was performed were included. NGS for KRAS, NRAS, and BRAF mutations using the AmpliSeq Cancer Hotspot Panel v2.0 kit (Thermo Fisher Scientific, Waltham, Massachusetts) was performed on cytology cell pellets. Results: Forty-eight cases were identified. Forty-six of 48 specimens (96%) were adequate for molecular testing. Of those adequate specimens, proportion of malignant cells in the sample ranged from 5% to 95% (mean 46%). Twenty-seven of 48 cases (56%) were positive for clinically relevant mutations. Twenty-four of 27 cases (89%) were positive for KRAS mutations, with exon 2 most frequently involved (22/24 cases, 92%). Two of 27 cases (7%) were positive for NRAS mutations and one case (1/27, 4%) was positive for a BRAF mutation involving codon 594. Conclusion: Mutational analysis performed on cytology cell pellets serves as a useful means of gathering clinically actionable information on tumor mutation status in metastatic CRC. K E Y W O R D S colorectal carcinoma, cytology, fine-needle aspiration, molecular diagnostic technique, targeted molecular therapy This study was presented in part at

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“…KRAS (exon 3, 4), NRAS (exon 2, 3, 4) and BRAF mutations are also predictive biomarkers [6] [7]. Also, recently, amphiregulin and epiregulin, which belong to the epidermal growth factor (EGF) family, were reported as predictive biomarkers of cetuximab [8] [9]. However, it is difficult to utilize these factors as biomarkers of efficacy in clinical use.…”

Section: Introductionmentioning

confidence: 99%

Clinical Predictors of Cetuximab for First-Line Therapy of Metastatic Colorectal Cancer: A Single Institutional Retrospective Study

Morishita¹,

Tanioka²,

Asano³

et al. 2017

JCT

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Predictive factors of cetuximab efficacy for metastatic colorectal cancer (mCRC) have not been sufficiently revealed. The present study aimed to explore new predictors. A total of 30 patients with KRAS exon 2 wild-type unresectable mCRC, who had been treated with cetuximab-based regimen as first-line therapy, were retrospectively analyzed. We assessed whether gender, age, primary tumor site, RAS genotype, the Eastern Cooperative Oncology Group Performance Status (ECOG PS), metastatic status, histological grade, carcinoembryonic antigen (CEA), treatment regimen, and oxaliplatin-based adjuvant chemotherapy at baseline were associated with cetuximab efficacy. Progression-free survival (PFS) and objective response rate (ORR) were evaluated and statistically analyzed. Analysis of PFS revealed that left-sided tumor and good PS had relevance to good results. PFS among patients with left-sided CRC was longer than that among those with right-sided CRC (median, 10.6 and 3.5 months, respectively). Patients with a PS of 0 -1 experienced significantly longer PFS than those with a PS of 2 -3 (median, 8.6 versus 1.3 months, respectively). In analysis of ORR, high histological grade and serum CEA level showed interaction with good effect. Patients with histological grade I/II cancer experienced better ORR than those with histological grade III/IV cancer (76% versus 20%, respectively). ORR among patients with serum CEA level higher than 5.0 ng/ml was significantly higher than that among those with lower serum levels (88% versus 38%, respectively). ECOG PS, tumor location, histological grade, and serum CEA level at baseline might be useful predictors of cetuximab efficacy in the first-line treatment of mCRC.

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Prognostic and predictive biomarkers in metastatic colorectal cancer anti-EGFR therapy

Abstract: This review focuses on the personalized treatment of mCRC and discusses the potential of new prognostic and predictive biomarkers in selecting patients treated with anti-EGFR therapy.

Cited by 60 publications

References 66 publications

¿Existen ventajas clínicas al evaluar el estado de los genes KRAS, NRAS, BRAF, PIK3CA, PTEN y HER2 en pacientes con cáncer colorrectal?

¿Existen ventajas clínicas al evaluar el estado de los genes KRAS, NRAS, BRAF, PIK3CA, PTEN y HER2 en pacientes con cáncer colorrectal?

Molecular testing in metastatic colorectal adenocarcinoma cytology cell pellets

Clinical Predictors of Cetuximab for First-Line Therapy of Metastatic Colorectal Cancer: A Single Institutional Retrospective Study

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