journal article Open Access May 03, 2023

Comprehensive Genomic Profiling and Therapeutic Implications for Patients with Advanced Cancers: The Experience of an Academic Hospital

Diagnostics Vol. 13 No. 9 pp. 1619 · MDPI AG
View at Publisher Save 10.3390/diagnostics13091619
Abstract
Next-generation sequencing (NGS) can be used to detect tumor-specific genomic alterations. This retrospective single-center study aims to assess the application of an extensive NGS panel to identify actionable alterations and initiate matched targeted treatment for patients with advanced cancer. We analyzed genomic alterations in solid tumor biopsies from 464 patients with advanced cancer with the Foundation Medicine assay (FoundationOne®CDx). Therapeutic implications were determined using the Memorial Sloan Kettering Precision Oncology Knowledge Base (OncoKB) classification. The FoundationOne®CDx was successfully applied in 464/521 patients (89%). The most common altered genes were TP53 (61%), KRAS (20%), CDKN2A (20%), TERT (16%), and APC (16%). Among the 419 patients with successfully analyzed tumor mutational burden (TMB), 43 patients presented with a high TMB (≥10 mutations/megabase). Out of the 126 patients with an actionable target, 40 patients received matched treatment (32%) of which 17 were within a clinical trial. This study shows that the application of NGS is feasible in an academic center and increases the detection of actionable alterations and identification of patients eligible for targeted treatment or immunotherapy regardless of tumor histology. Strategies such as early referral for NGS, inclusion in clinical (basket) trials, and the development of new targeted drugs are necessary to improve the matched treatment rate.
Topics

No keywords indexed for this article. Browse by subject →

References
60
[1]
Slatko "Overview of Next-Generation Sequencing Technologies" Curr. Protoc. Mol. Biol. (2018) 10.1002/cpmb.59
[2]
Mateo "Delivering precision oncology to patients with cancer" Nat. Med. (2022) 10.1038/s41591-022-01717-2
[3]
(2022, August 10). Novel Drug Approvals for 2021, Available online: https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2021.
[4]
(2022, August 10). List of EMA-Approved Medicines. Available online: https://www.ema.europa.eu/en/medicines/ema_group_types/ema_medicine/field_ema_web_categories%253Aname_field/Human/field_ema_med_status/authorised-36.
[5]
Andre "Prioritizing targets for precision cancer medicine" Ann. Oncol. (2014) 10.1093/annonc/mdu478
[6]
Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials

Robert C Doebele, Alexander Drilon, Luis Paz-Ares et al.

The Lancet Oncology 2020 10.1016/s1470-2045(19)30691-6
[7]
Loriot "Tumor agnostic efficacy and safety of erdafitinib in patients (pts) with advanced solid tumors with prespecified fibroblast growth factor receptor alterations (FGFRalt) in RAGNAR: Interim analysis (IA) results" J. Clin. Oncol. (2022) 10.1200/jco.2022.40.16_suppl.3007
[8]
Kato "Real-world data from a molecular tumor board demonstrates improved outcomes with a precision N-of-One strategy" Nat. Commun. (2020) 10.1038/s41467-020-18613-3
[9]
Merlin "Targeted PCR vs. NGS for molecular diagnostic in solid tumors and liquid biopsies. How to choose in real-life" J. Clin. Oncol. (2020) 10.1200/jco.2020.38.15_suppl.e15576
[10]
Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma

Apinya Jusakul, Ioana Cutcutache, Chern Han Yong et al.

Cancer Discovery 2017 10.1158/2159-8290.cd-17-0368
[11]
Milbury, C.A., Creeden, J., Yip, W.K., Smith, D.L., Pattani, V., Maxwell, K., Sawchyn, B., Gjoerup, O., Meng, W., and Skoletsky, J. (2022). Clinical and analytical validation of FoundationOne®CDx, a comprehensive genomic profiling assay for solid tumors. PLoS ONE, 17. 10.1371/journal.pone.0264138
[12]
Colomer "When should we order a next generation sequencing test in a patient with cancer?" EClinicalMedicine (2020) 10.1016/j.eclinm.2020.100487
[13]
Mosele "Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: A report from the ESMO Precision Medicine Working Group" Ann. Oncol. (2020) 10.1016/j.annonc.2020.07.014
[14]
Kamal "Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials" J. Natl. Cancer Inst. (2016) 10.1093/jnci/djv362
[15]
Karol "The Impact of Foundation Medicine Testing on Cancer Patients: A Single Academic Centre Experience" Front. Oncol. (2021) 10.3389/fonc.2021.687730
[16]
Bachelot "Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: A multicentre, prospective trial (SAFIR01/UNICANCER)" Lancet Oncol. (2014) 10.1016/s1470-2045(13)70611-9
[17]
Brusco "Feasibility of Large-Scale Genomic Testing to Facilitate Enrollment Onto Genomically Matched Clinical Trials" J. Clin. Oncol. (2015) 10.1200/jco.2014.60.4165
[18]
Sohal "Prospective Clinical Study of Precision Oncology in Solid Tumors" J. Natl. Cancer Inst. (2015)
[19]
Nagahashi "Next generation sequencing-based gene panel tests for the management of solid tumors" Cancer Sci. (2019) 10.1111/cas.13837
[20]
FDA (2023, April 27). FDA Grants Marketing Approval to FoundationOne CDx In Vitro Diagnostic 2017, Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-marketing-approval-foundationone-cdx-in-vitro-diagnostic.
[21]
Karlovich "Clinical Applications of Next-Generation Sequencing in Precision Oncology" Cancer J. (2019) 10.1097/ppo.0000000000000385
[22]
Medicine, F. (2023, April 27). Technical Specification. Available online: https://info.foundationmedicine.com/hubfs/FMI%20Labels/FoundationOne_CDx_Label_Technical_Info.pdf.
[23]
Post, T.A. (2023, April 27). FDA Authorizes MSK-IMPACT Tumor Profiling Assay. Available online: https://ascopost.com/News/58263.
[24]
Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients

Ahmet Zehir, Ryma Benayed, Ronak H Shah et al.

Nature Medicine 2017 10.1038/nm.4333
[25]
Center, M.S.K.C. (2023, April 27). MSK-IMPACT: A Targeted Test for Mutations in Both Rare and Common Cancers. Available online: https://www.mskcc.org/msk-impact.
[26]
"The current landscape of the FDA approved companion diagnostics" Transl. Oncol. (2021) 10.1016/j.tranon.2021.101063
[27]
Wakai "Precision Cancer Medicine and Super-computing System" Keio J. Med. (2017) 10.2302/kjm.66-003-abst
[28]
Conroy "Analytical Validation of a Next-Generation Sequencing Assay to Monitor Immune Responses in Solid Tumors" J. Mol. Diagn. (2018) 10.1016/j.jmoldx.2017.10.001
[29]
OncoKB: A Precision Oncology Knowledge Base

Debyani Chakravarty, Jianjiong Gao, Sarah Phillips et al.

JCO Precision Oncology 10.1200/po.17.00011
[30]
Takeda "Clinical Application of the FoundationOne CDx Assay to Therapeutic Decision-Making for Patients with Advanced Solid Tumors" Oncologist (2021) 10.1002/onco.13639
[31]
Gambardella "Molecular profiling of advanced solid tumours. The impact of experimental molecular-matched therapies on cancer patient outcomes in early-phase trials: The MAST study" Br. J. Cancer (2021) 10.1038/s41416-021-01502-x
[32]
Flaherty "The Molecular Analysis for Therapy Choice (NCI-MATCH) Trial: Lessons for Genomic Trial Design" J. Natl. Cancer Inst. (2020) 10.1093/jnci/djz245
[34]
Coquerelle "Impact of Next Generation Sequencing on Clinical Practice in Oncology in France: Better Genetic Profiles for Patients Improve Access to Experimental Treatments" Value Health (2020) 10.1016/j.jval.2020.03.005
[35]
Delord "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" Lancet Oncol. (2015) 10.1016/s1470-2045(15)00188-6
[37]
Prasad "Characteristics of Exceptional or Super Responders to Cancer Drugs" Mayo Clin. Proc. (2015) 10.1016/j.mayocp.2015.08.017
[38]
Smith "Accessing Targeted Therapies: A Potential Roadblock to Implementing Precision Oncology?" JCO Oncol. Pract. (2021) 10.1200/op.20.00927
[39]
Garralda "New clinical trial designs in the era of precision medicine" Mol. Oncol. (2019) 10.1002/1878-0261.12465
[40]
Reitsma "Effect of a Collaboration Between a Health Plan, Oncology Practice, and Comprehensive Genomic Profiling Company from the Payer Perspective" J. Manag. Care Spec. Pharm. (2019)
[41]
Rationale and Design of the Targeted Agent and Profiling Utilization Registry Study

Pam K. Mangat, Susan Halabi, Suanna S. Bruinooge et al.

JCO Precision Oncology 2018 10.1200/po.18.00122
[42]
ClinicalTrials.gov (2022, December 17). A Danish Nationwide Clinical Trial on Targeted Cancer Treatment Based on Genomic Profiling (ProTarget), Available online: https://clinicaltrials.gov/ct2/show/NCT04341181.
[43]
ClinicalTrials.gov (2022, December 17). A MolEcularly Guided Anti-Cancer Drug Off-Label Trial (MEGALiT), Available online: https://clinicaltrials.gov/ct2/show/NCT04185831.
[44]
Drilon "Tumor-agnostic precision immuno-oncology and somatic targeting rationale for you (TAPISTRY): A novel platform umbrella trial" J. Clin. Oncol. (2021) 10.1200/jco.2021.39.15_suppl.tps3154
[45]
Clinicaltrials.gov (2022, December 17). A Study to Examine the Clinical Value of Comprehensive Genomic Profiling Performed by Belgian NGS Laboratories: A Belgian Precision Study of the BSMO in Collaboration With the Cancer Centre (BALLETT), Available online: https://clinicaltrials.gov/ct2/show/NCT05058937.
[46]
Clinicaltrials.gov (2022, December 17). Initiative for Molecular Profiling and Advanced Cancer Therapy (IMPACT II), Available online: https://www.clinicaltrials.gov/ct2/show/NCT02152254.
[47]
Clinicaltrials.gov (2022, December 17). PREcision Medicine in Cancer in Odense, Denmark (PRECODE), Available online: https://clinicaltrials.gov/ct2/show/NCT05385081.
[48]
Blay "PROFILER 02—A multicentric, prospective cohort study aiming to evaluate the added value of a large molecular profiling panel (315 cancer-related gene panel [FoundationOne]) versus a limited molecular profiling panel (74 cancer-related gene panel [CONTROL]) in advanced solid tumours" Ann. Oncol. (2017) 10.1093/annonc/mdx508.004
[49]
Skamene "Canadian profiling and targeted agent utilization trial (CAPTUR/PM.1): A phase II basket precision medicine trial" J. Clin. Oncol. (2018) 10.1200/jco.2018.36.15_suppl.tps12127
[50]
Massard "High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial" Cancer Discov. (2017) 10.1158/2159-8290.cd-16-1396

Showing 50 of 60 references