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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

24.3K

Next-generation sequencing-based evaluation of the actionable landscape of genomic alterations in solid tumors: the

Francesco Schettini1,2,3, Marianna Sirico4, Marco Loddo5

  • 1Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.

The Oncologist
|August 23, 2024
PubMed
Abstract

Insights

Molecular profiling of advanced cancers using next-generation sequencing (NGS) identified actionable genomic alterations in most tumors. However, treatment response varied, underscoring the need for tumor-specific interpretation of genetic findings.

Area of Science:

  • Oncology
  • Genomics
  • Precision Medicine

Background:

  • Targeted therapy selection for advanced cancers remains a clinical challenge.
  • Molecular profiling via comprehensive next-generation sequencing (NGS) can identify genomic alterations.
  • Assessing correlations between genomic alterations, PD-L1 expression, and treatment outcomes is crucial.

Purpose of the Study:

  • To determine the type, frequency, and actionability of genomic alterations in metastatic solid tumors.
  • To explore potential correlations between these alterations and PD-L1 expression.
  • To evaluate the clinical utility of molecular profiling in guiding treatment decisions.

Main Methods:

  • Conducted molecular profiling on 304 heavily pretreated metastatic cancer patients using a 505-gene NGS assay (Oncofocus).
  • Analyzed newly obtained or archived tumor biopsies.
  • Employed statistical tests (Chi-square, Kruskal-Wallis, Wilcoxon rank-sum) with significance at P < .05.

Main Results:

  • 78% of tumors (237/304) exhibited potentially actionable genomic alterations.
  • 68.9% of tumors were positive for PD-L1 expression.
  • DNA damage repair (14%), PI3K/AKT/mTOR (14%), and RAS/RAF/MAPK (12%) pathways were most frequently altered.
  • Only 34.5% of alterations were actionable (ESCAT Tier I-II).
  • No significant association found between PD-L1, ESCAT status, age, sex, or mutational burden.
  • 37.1% objective response rate observed in 62 patients receiving molecularly guided treatment.
  • Clinical outcomes varied even with similar molecular-targeted treatments across different cancer types.

Conclusions:

  • Comprehensive NGS-based molecular profiling is valuable for refining treatment strategies in advanced solid tumors.
  • Facilitates patient stratification for clinical trials.
  • Emphasizes the critical need for tumor type-specific interpretation of genomic alterations for effective treatment.
Keywords:
ESCATclinical actionabilitymetastaticmolecular profilingnext-generation sequencingsolid tumors

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