Federica Morano

V600EBRAF mutated metastatic colorectal cancer (mCRC) is a subtype (10%) with overall poor prognosis, but the clinical experience suggests a great heterogeneity in survival. It is still unexplored the real distribution of traditional and innovative biomarkers among V600EBRAF mutated mCRC and which is their role in the improvement of clinical prediction of survival outcomes.Data and tissue specimens from 155 V600EBRAF mutated mCRC patients treated at eight Italian Units of Oncology were collected. Specimens were analysed by means of immunohistochemistry profiling performed on tissue microarrays. Primary endpoint was overall survival (OS).CDX2 loss conferred worse OS (HR = 1.72, 95%CI 1.03-2.86, p = 0.036), as well as high CK7 expression (HR = 2.17, 95%CI 1.10-4.29, p = 0.026). According to Consensus Molecular Subtypes (CMS), CMS1 patients had better OS compared to CMS2-3/CMS4 (HR = 0.37, 95%CI 0.19-0.71, p = 0.003). Samples showing less TILs had worse OS (HR = 1.72, 95%CI 1.16-2.56, p = 0.007). Progression-free survival analyses led to similar results. At multivariate analysis, CK7 and CMS subgrouping retained their significant correlation with OS.The present study provides new evidence on how several well-established biomarkers perform in a homogenousV600EBRAF mutated mCRC population, with important and independent information added to standard clinical prognosticators. These data could be useful to inform further translational research, for patients' stratification in clinical trials and in routine clinical practice to better estimate patients' prognosis.

Tissue microarray

Clinical endpoint

Molecular biomarkers

10.1038/s41416-019-0560-0

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Citations (30)

Supplementary Figure S3 from An Immune-Related Gene Expression Signature Predicts Benefit from Adding Atezolizumab to FOLFOXIRI plus Bevacizumab in Metastatic Colorectal Cancer

Carlotta Antoniotti Alessandra Boccaccino Robert S. Seitz Mirella Giordano Aurélie Catteau

Kaplan Meier estimates of progression-free survival in the pMMR population (optimized cut-point), according to IO status (a) and to both IO status and treatment arm (b). Legend: HR: hazard ratio, NR: not reached. Control arm indicates FOLFOXIRI plus bevacizumab. Atezo arm indicates FOLFOXIRI plus bevacizumab and atezolizumab.

Atezolizumab

Gene signature

Clinical endpoint

10.1158/1078-0432.22692639.v1

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Citations (0)

Supplementary Figure S2 from An Immune-Related Gene Expression Signature Predicts Benefit from Adding Atezolizumab to FOLFOXIRI plus Bevacizumab in Metastatic Colorectal Cancer

Carlotta Antoniotti Alessandra Boccaccino Robert S. Seitz Mirella Giordano Aurélie Catteau

Kaplan Meier estimates of progression-free survival in the overall population (optimized cut-point), according to IO status (a) and to both IO status and treatment arm (b). Legend: HR: hazard ratio, NR: not reached. Control arm indicates FOLFOXIRI plus bevacizumab. Atezo arm indicates FOLFOXIRI plus bevacizumab and atezolizumab.

Atezolizumab

Clinical endpoint

Gene signature

10.1158/1078-0432.22692642

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Supplementary Figure S3 from An Immune-Related Gene Expression Signature Predicts Benefit from Adding Atezolizumab to FOLFOXIRI plus Bevacizumab in Metastatic Colorectal Cancer

Carlotta Antoniotti Alessandra Boccaccino Robert S. Seitz Mirella Giordano Aurélie Catteau

Kaplan Meier estimates of progression-free survival in the pMMR population (optimized cut-point), according to IO status (a) and to both IO status and treatment arm (b).Legend: HR: hazard ratio, NR: not reached. Control arm indicates FOLFOXIRI plus bevacizumab. Atezo arm indicates FOLFOXIRI plus bevacizumab and atezolizumab.

Atezolizumab

Gene signature

Clinical endpoint

10.1158/1078-0432.23507152.v1

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Supplementary Methods1 from HER2 Copy Number and Resistance Mechanisms in Patients with HER2-positive Advanced Gastric Cancer Receiving Initial Trastuzumab-based Therapy in JACOB Trial

Filippo Pietrantonio Paolo Manca Sara E. Bellomo Simona Corso Alessandra Raimondi

Supplementary Methods

Pertuzumab

10.1158/1078-0432.22490099.v1

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