sábado, 3 de noviembre de 2018

Prospective Genotyping of Hepatocellular Carcinoma: Clinical Implications of Next Generation Sequencing for Matching Patients to Targeted and Immun... - PubMed - NCBI

Prospective Genotyping of Hepatocellular Carcinoma: Clinical Implications of Next Generation Sequencing for Matching Patients to Targeted and Immun... - PubMed - NCBI



 2018 Oct 29. pii: clincanres.2293.2018. doi: 10.1158/1078-0432.CCR-18-2293. [Epub ahead of print]

Prospective Genotyping of Hepatocellular Carcinoma: Clinical Implications of Next Generation Sequencing for Matching Patients to Targeted and Immune Therapies.

Abstract

PURPOSE:

Prior molecular profiling of hepatocellular carcinoma (HCC) has identified actionable findings that may have a role in guiding therapeutic decision-making and clinical trial enrollment. We implemented prospective next-generation sequencing (NGS) in the clinic to determine whether such analyses provide predictive and/or prognostic information for HCC patients treated with contemporary systemic therapies.

METHODS:

Matched tumor/normal DNA from HCC patients (N=127) were analyzed using a hybridization capture-based, NGS assay designed to target 341 or more cancer-associated genes. Demographic and treatment data were prospectively collected with the goal of correlating treatment outcomes and drug response with molecular profiles.

RESULTS:

WNT/β-catenin pathway (45%) and TP53 (35%) alterations were frequent and represented mutually exclusive molecular subsets. In sorafenib treated patients (N=81), oncogenic PI3K-MTOR pathway alterations were associated with lower disease control rates (DCR, 8.3 vs. 40.2%), shorter median PFS (1.9 vs 5.3 months) and OS (10.4 vs 17.9 months). For patients treated with immune checkpoint inhibitors (N=31), activating alteration WNT/β-catenin signaling were associated with lower DCR (0 vs 53%), shorter median PFS (2.0 vs 7.4 months) and OS (9.1 vs 15.2 months). 24% of patients harbored potentially actionable alterations including TSC1/2 (8.5%)inactivating/truncating mutations, FGF19 (6.3%) and MET (1.5%) amplifications, and IDH1 missense mutations (<1%). 6% of patients treated with systemic therapy were matched to targeted therapeutics.

CONCLUSION:

Linking NGS to routine clinical care has the potential to identify those HCC patients likely to benefit from standard systemic therapies and can be used in an investigational context to match patients to genome-directed targeted therapies.

PMID:
 
30373752
 
DOI:
 
10.1158/1078-0432.CCR-18-2293

No hay comentarios:

Publicar un comentario