Assessment of Clinical Benefit of Integrative Genomic Profiling in Advanced Solid Tumors

Key Points Question What is the clinical utility of genomic profiling for patients with advanced solid tumors? Findings In this cohort study of 1015 patients who underwent integrative genomic profiling, a high rate of pathogenic germline variants and a subset of patients who derive substantial clinical benefit from sequencing information were identified. Meaning These findings support (1) directed germline testing for inherited cancer predisposition in all patients with advanced cancer and (2) use of integrative genomic profiling as a component of standard of care for patients with cancer of unknown origin and other rare malignant neoplasms.

[1]  David J. Sims,et al.  Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  Alex H. Wagner,et al.  A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer , 2020, Nature Genetics.

[3]  L. Diaz,et al.  Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  Ying Cheng,et al.  Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. , 2019, The New England journal of medicine.

[5]  J Jack Lee,et al.  Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial , 2019, Nature Medicine.

[6]  F. Nielsen,et al.  Copenhagen Prospective Personalized Oncology (CoPPO)—Clinical Utility of Using Molecular Profiling to Select Patients to Phase I Trials , 2018, Clinical Cancer Research.

[7]  N. Schultz,et al.  A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) , 2018, Annals of oncology : official journal of the European Society for Medical Oncology.

[8]  Edward S. Kim,et al.  Rationale and Design of the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. , 2018, JCO precision oncology.

[9]  Ying Cheng,et al.  Osimertinib in Untreated EGFR‐Mutated Advanced Non–Small‐Cell Lung Cancer , 2018, The New England journal of medicine.

[10]  Ludmila V. Danilova,et al.  Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade , 2017, Science.

[11]  Robert J. Lonigro,et al.  Integrative Clinical Genomics of Metastatic Cancer , 2017, Nature.

[12]  Marie-Cécile Le Deley,et al.  High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial. , 2017, Cancer discovery.

[13]  K. Hess,et al.  Initiative for Molecular Profiling and Advanced Cancer Therapy (IMPACT): An MD Anderson Precision Medicine Study. , 2017, JCO precision oncology.

[14]  Moriah H Nissan,et al.  OncoKB: A Precision Oncology Knowledge Base. , 2017, JCO precision oncology.

[15]  Donavan T. Cheng,et al.  Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients , 2017, Nature Medicine.

[16]  Marilyn M. Li,et al.  Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. , 2017, The Journal of molecular diagnostics : JMD.

[17]  Marian Harris,et al.  Institutional implementation of clinical tumor profiling on an unselected cancer population. , 2016, JCI insight.

[18]  Milan Radovich,et al.  Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers , 2016, Oncotarget.

[19]  R. Yelensky,et al.  Cancer Therapy Directed by Comprehensive Genomic Profiling: A Single Center Study. , 2016, Cancer research.

[20]  S. Lippman,et al.  Precision Oncology: The UC San Diego Moores Cancer Center PREDICT Experience , 2016, Molecular Cancer Therapeutics.

[21]  Nicolas Servant,et al.  Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. , 2015, The Lancet. Oncology.

[22]  A. Chen,et al.  An overview of the NCI precision medicine trials-NCI MATCH and MPACT. , 2015, Chinese clinical oncology.

[23]  Vladimir Vacic,et al.  Whole-Exome Sequencing of Metastatic Cancer and Biomarkers of Treatment Response. , 2015, JAMA oncology.

[24]  Funda Meric-Bernstam,et al.  Feasibility of Large-Scale Genomic Testing to Facilitate Enrollment Onto Genomically Matched Clinical Trials. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  R. Kurzrock,et al.  On the Road to Precision Cancer Medicine: Analysis of Genomic Biomarker Actionability in 439 Patients , 2015, Molecular Cancer Therapeutics.

[26]  Razelle Kurzrock,et al.  Personalized Medicine for Patients with Advanced Cancer in the Phase I Program at MD Anderson: Validation and Landmark Analyses , 2014, Clinical Cancer Research.

[27]  J. Doroshow,et al.  Molecular analysis for therapy choice: NCI MATCH. , 2014, Seminars in oncology.

[28]  Niels Richard Hansen,et al.  Modeling tissue contamination to improve molecular identification of the primary tumor site of metastases , 2014, Bioinform..

[29]  Alex M. Fichtenholtz,et al.  Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing , 2013, Nature Biotechnology.

[30]  K. Flaherty,et al.  Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. , 2012, The New England journal of medicine.

[31]  L. Moja,et al.  Trastuzumab containing regimens for early breast cancer. , 2012, The Cochrane database of systematic reviews.

[32]  Lee T. Sam,et al.  Personalized Oncology Through Integrative High-Throughput Sequencing: A Pilot Study , 2011, Science Translational Medicine.

[33]  T. Fleming,et al.  Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. , 2001, The New England journal of medicine.