Real-World Performance of a Comprehensive Genomic Profiling Test Optimized for Small Tumor Samples
Scott A Tomlins, Daniel H Hovelson, Jennifer M Suga, Daniel M Anderson, Han A Koh, Elizabeth C Dees, Brendan McNulty, Mark E Burkard, Michael Guarino, Jamil Khatri, Malek M Safa, Marc R Matrana, Eddy S Yang, Alex R Menter, Benjamin M Parsons, Jennifer N Slim, Michael A Thompson, Leon Hwang, William J Edenfield, Suresh Nair, Adedayo Onitilo, Robert Siegel, Alan Miller, Timothy Wassenaar, William J Irvin, William Schulz, Arvinda Padmanabhan, Vallathucherry Harish, Anneliese Gonzalez, Abdul Hai Mansoor, Andrew Kellum, Paul Harms, Stephanie Drewery, Jayson Falkner, Andrew Fischer, Jennifer Hipp, Kat Kwiatkowski, Lorena Lazo de la Vega, Khalis Mitchell, Travis Reeder, Javed Siddiqui, Hana Vakil, D Bryan Johnson, Daniel R Rhodes, Scott A Tomlins, Daniel H Hovelson, Jennifer M Suga, Daniel M Anderson, Han A Koh, Elizabeth C Dees, Brendan McNulty, Mark E Burkard, Michael Guarino, Jamil Khatri, Malek M Safa, Marc R Matrana, Eddy S Yang, Alex R Menter, Benjamin M Parsons, Jennifer N Slim, Michael A Thompson, Leon Hwang, William J Edenfield, Suresh Nair, Adedayo Onitilo, Robert Siegel, Alan Miller, Timothy Wassenaar, William J Irvin, William Schulz, Arvinda Padmanabhan, Vallathucherry Harish, Anneliese Gonzalez, Abdul Hai Mansoor, Andrew Kellum, Paul Harms, Stephanie Drewery, Jayson Falkner, Andrew Fischer, Jennifer Hipp, Kat Kwiatkowski, Lorena Lazo de la Vega, Khalis Mitchell, Travis Reeder, Javed Siddiqui, Hana Vakil, D Bryan Johnson, Daniel R Rhodes
Abstract
Purpose: Tissue-based comprehensive genomic profiling (CGP) is increasingly used for treatment selection in patients with advanced cancer; however, tissue availability may limit widespread implementation. Here, we established real-world CGP tissue availability and assessed CGP performance on consecutively received samples.
Materials and methods: We conducted a post hoc, nonprespecified analysis of 32,048 consecutive tumor tissue samples received for StrataNGS, a multiplex polymerase chain reaction (PCR)-based comprehensive genomic profiling (PCR-CGP) test, as part of an ongoing observational trial (NCT03061305). Sample characteristics and PCR-CGP performance were assessed across all tested samples, including exception samples not meeting minimum input quality control (QC) requirements (< 20% tumor content [TC], < 2 mm2 tumor surface area [TSA], DNA or RNA yield < 1 ng/µL, or specimen age > 5 years). Tests reporting ≥ 1 prioritized alteration or meeting TC and sequencing QC were considered successful. For prostate carcinoma and lung adenocarcinoma, tests reporting ≥ 1 actionable or informative alteration or meeting TC and sequencing QC were considered actionable.
Results: Among 31,165 (97.2%) samples where PCR-CGP was attempted, 10.7% had < 20% TC and 59.2% were small (< 25 mm2 tumor surface area). Of 31,101 samples evaluable for input requirements, 8,089 (26.0%) were exceptions not meeting requirements. However, 94.2% of the 31,101 tested samples were successfully reported, including 80.5% of exception samples. Positive predictive value of PCR-CGP for ERBB2 amplification in exceptions and/or sequencing QC-failure breast cancer samples was 96.7%. Importantly, 84.0% of tested prostate carcinomas and 87.9% of lung adenocarcinomas yielded results informing treatment selection.
Conclusion: Most real-world tissue samples from patients with advanced cancer desiring CGP are limited, requiring optimized CGP approaches to produce meaningful results. An optimized PCR-CGP test, coupled with an inclusive exception testing policy, delivered reportable results for > 94% of samples, potentially expanding the proportion of CGP-testable patients and impact of biomarker-guided therapies.
Conflict of interest statement
Scott A. Tomlins Employment: Strata Oncology Leadership: Strata Oncology Stock and Other Ownership Interests: Strata Oncology, Javelin Oncology Consulting or Advisory Role: Janssen, Astellas Medivation, Strata Oncology Research Funding: Astellas Medivation Patents, Royalties, Other Intellectual Property: I am a coinventor on a patent issued to the University of Michigan on ETS gene fusions in prostate and am included in the royalty stream. The diagnostic field of use was licensed to Hologic/Gen-Probe (who sublicensed some rights to Ventana/Roche) and is licensed to LynxDx. I am a coinventor on a patent issued to Strata Oncology related to MSI determination and checkpoint inhibitor benefit Travel, Accommodations, Expenses: Strata Oncology, Genzyme Daniel H. Hovelson Employment: Strata Oncology Elizabeth C. Dees Consulting or Advisory Role: Novartis, Strata Oncology, G1 Therapeutics Research Funding: Novartis, Genentech/Roche, Pfizer, Merck, H3 Biomedicine, Meryx Pharmaceuticals Travel, Accommodations, Expenses: G1 Therapeutics Mark E. Burkard Consulting or Advisory Role: Pointcare genomics, Strata Oncology, Novartis Research Funding: AbbVie, Strata Oncology, Puma Biotechnology, Loxo, Merck, Arcus Ventures, Apollomics, Elevation Oncology, Genentech Patents, Royalties, Other Intellectual Property: I have a patent for implantable/localized drug delivery device that can sample the tumor microenvironment and deliver drug, I have a patent for a method to detect recombination events with CRISPR-mediated editing, and I have a patent for conducting expansion microscopy without specialized equipment Michael Guarino Stock and Other Ownership Interests: Johnson and Johnson, Johnson and Johnson Travel, Accommodations, Expenses: McKesson, ARMO BioSciences, AstraZeneca, BMS, De Novo Pharmaceuticals Marc R. Matrana Consulting or Advisory Role: Strata Oncology Speakers' Bureau: Bristol Myers Squibb, AstraZeneca, Merck, Eisai, Genentech, Janssen, Exelixis Eddy S. Yang Consulting or Advisory Role: Strata Oncology, AstraZeneca, Bayer, Clovis Oncology, Lilly Research Funding: Lilly, Novartis, Clovis Oncology, Puma Biotechnology Benjamin M. Parsons Consulting or Advisory Role: Celgene, Amgen, AstraZeneca Speakers' Bureau: Amgen, Celgene, AstraZeneca Open Payments Link: https://openpaymentsdata.cms.gov/physician/795031 Michael A. Thompson Stock and Other Ownership Interests: Doximity Consulting or Advisory Role: Celgene, VIA Oncology, Takeda, GlaxoSmithKline, Strata Oncology, Syapse, Adaptive Biotechnologies, AbbVie, GRAIL, Epizyme, Janssen Oncology Research Funding: Takeda, Bristol Myers Squibb, TG Therapeutics, Cancer Research and Biostatistics, AbbVie, PrECOG, Strata Oncology, Lynx Biosciences, Denovo Biopharma, ARMO BioSciences, GlaxoSmithKline, Amgen Patents, Royalties, Other Intellectual Property: UpToDate, Peer Review for Plasma Cell Dyscrasias (Editor: Robert Kyle) Travel, Accommodations, Expenses: Takeda, GlaxoSmithKline, Syapse Other Relationship: Doximity Open Payments Link: https://openpaymentsdata.cms.gov/physician/192826/summary William J. Edenfield Consulting or Advisory Role: Chimerix Suresh Nair Stock and Other Ownership Interests: Moderna Therapeutics, Novavax, Biontech, Gilead Sciences Research Funding: Bristol Myers Squibb, Merck, Nektar Adedayo Onitilo Consulting or Advisory Role: Kite, a Gilead company, Envision Communications Speakers' Bureau: GlaxoSmithKline, Puma Biotechnology, Kite/Gilead, AbbVie Robert Siegel Research Funding: Merck, Mirati Therapeutics, GRAIL, Altor BioScience, Galera Therapeutics, Apollomics, Strata Oncology, Arcus Biosciences, Bristol Myers Squibb, Cancer Insight, Puma Biotechnology, Conjupro Biotherapeutics, Razor Genomics, Sanofi, Seattle Genetics Other Relationship: American Board of Internal Medicine (ABIM) William J. Irvin Research Funding: Merck, Altor BioScience, Odonate Therapeutics, Boston Biomedical, Novartis, Pfizer, Seattle Genetics, Altor BioScience, AstraZeneca Arvinda Padmanabhan Speakers' Bureau: Clovis Oncology, Roche Anneliese Gonzalez Research Funding: Novartis, Radius Health, Astellas Pharma Paul Harms Research Funding: Q32 Bio Jennifer Hipp Employment: Strata Oncology Stock and Other Ownership Interests: Strata Oncology Consulting or Advisory Role: PathAI Kat Kwiatkowski Employment: Strata Oncology Stock and Other Ownership Interests: Strata Oncology, Epizyme, Loxo, Editas Medicine, Intuitive Surgical Khalis Mitchell Employment: Strata Oncology Stock and Other Ownership Interests: Mirati Therapeutics Javed Siddiqui Consulting or Advisory Role: Strata Oncology, LynxDx Hana Vakil Employment: Strata Oncology Stock and Other Ownership Interests: Strata Oncology D. Bryan Johnson Employment: Strata Oncology Stock and Other Ownership Interests: Strata Oncology Daniel R. Rhodes Employment: Strata Oncology, Javelin Oncology Leadership: Strata Oncology, Javelin Oncology Stock and Other Ownership Interests: Strata Oncology, Javelin Oncology Patents, Royalties, Other Intellectual Property: I am paid royalties from the University of Michigan on license revenues related to a patent on prostate cancer gene fusions No other potential conflicts of interest were reported. Scott A. Tomlins Employment: Strata Oncology Leadership: Strata Oncology Stock and Other Ownership Interests: Strata Oncology, Javelin Oncology Consulting or Advisory Role: Janssen, Astellas Medivation, Strata Oncology Research Funding: Astellas Medivation Patents, Royalties, Other Intellectual Property: I am a coinventor on a patent issued to the University of Michigan on ETS gene fusions in prostate and am included in the royalty stream. The diagnostic field of use was licensed to Hologic/Gen-Probe (who sublicensed some rights to Ventana/Roche) and is licensed to LynxDx. I am a coinventor on a patent issued to Strata Oncology related to MSI determination and checkpoint inhibitor benefit Travel, Accommodations, Expenses: Strata Oncology, Genzyme Daniel H. Hovelson Employment: Strata Oncology Elizabeth C. Dees Consulting or Advisory Role: Novartis, Strata Oncology, G1 Therapeutics Research Funding: Novartis, Genentech/Roche, Pfizer, Merck, H3 Biomedicine, Meryx Pharmaceuticals Travel, Accommodations, Expenses: G1 Therapeutics Mark E. Burkard Consulting or Advisory Role: Pointcare genomics, Strata Oncology, Novartis Research Funding: AbbVie, Strata Oncology, Puma Biotechnology, Loxo, Merck, Arcus Ventures, Apollomics, Elevation Oncology, Genentech Patents, Royalties, Other Intellectual Property: I have a patent for implantable/localized drug delivery device that can sample the tumor microenvironment and deliver drug, I have a patent for a method to detect recombination events with CRISPR-mediated editing, and I have a patent for conducting expansion microscopy without specialized equipment Michael Guarino Stock and Other Ownership Interests: Johnson and Johnson, Johnson and Johnson Travel, Accommodations, Expenses: McKesson, ARMO BioSciences, AstraZeneca, BMS, De Novo Pharmaceuticals Marc R. Matrana Consulting or Advisory Role: Strata Oncology Speakers' Bureau: Bristol Myers Squibb, AstraZeneca, Merck, Eisai, Genentech, Janssen, Exelixis Eddy S. Yang Consulting or Advisory Role: Strata Oncology, AstraZeneca, Bayer, Clovis Oncology, Lilly Research Funding: Lilly, Novartis, Clovis Oncology, Puma Biotechnology Benjamin M. Parsons Consulting or Advisory Role: Celgene, Amgen, AstraZeneca Speakers' Bureau: Amgen, Celgene, AstraZeneca Open Payments Link: https://openpaymentsdata.cms.gov/physician/795031 Michael A. Thompson Stock and Other Ownership Interests: Doximity Consulting or Advisory Role: Celgene, VIA Oncology, Takeda, GlaxoSmithKline, Strata Oncology, Syapse, Adaptive Biotechnologies, AbbVie, GRAIL, Epizyme, Janssen Oncology Research Funding: Takeda, Bristol Myers Squibb, TG Therapeutics, Cancer Research and Biostatistics, AbbVie, PrECOG, Strata Oncology, Lynx Biosciences, Denovo Biopharma, ARMO BioSciences, GlaxoSmithKline, Amgen Patents, Royalties, Other Intellectual Property: UpToDate, Peer Review for Plasma Cell Dyscrasias (Editor: Robert Kyle) Travel, Accommodations, Expenses: Takeda, GlaxoSmithKline, Syapse Other Relationship: Doximity Open Payments Link: https://openpaymentsdata.cms.gov/physician/192826/summary William J. Edenfield Consulting or Advisory Role: Chimerix Suresh Nair Stock and Other Ownership Interests: Moderna Therapeutics, Novavax, Biontech, Gilead Sciences Research Funding: Bristol Myers Squibb, Merck, Nektar Adedayo Onitilo Consulting or Advisory Role: Kite, a Gilead company, Envision Communications Speakers' Bureau: GlaxoSmithKline, Puma Biotechnology, Kite/Gilead, AbbVie Robert Siegel Research Funding: Merck, Mirati Therapeutics, GRAIL, Altor BioScience, Galera Therapeutics, Apollomics, Strata Oncology, Arcus Biosciences, Bristol Myers Squibb, Cancer Insight, Puma Biotechnology, Conjupro Biotherapeutics, Razor Genomics, Sanofi, Seattle Genetics Other Relationship: American Board of Internal Medicine (ABIM) William J. Irvin Research Funding: Merck, Altor BioScience, Odonate Therapeutics, Boston Biomedical, Novartis, Pfizer, Seattle Genetics, Altor BioScience, AstraZeneca Arvinda Padmanabhan Speakers' Bureau: Clovis Oncology, Roche Anneliese Gonzalez Research Funding: Novartis, Radius Health, Astellas Pharma Paul Harms Research Funding: Q32 Bio Jennifer Hipp Employment: Strata Oncology Stock and Other Ownership Interests: Strata Oncology Consulting or Advisory Role: PathAI Kat Kwiatkowski Employment: Strata Oncology Stock and Other Ownership Interests: Strata Oncology, Epizyme, Loxo, Editas Medicine, Intuitive Surgical Khalis Mitchell Employment: Strata Oncology Stock and Other Ownership Interests: Mirati Therapeutics Javed Siddiqui Consulting or Advisory Role: Strata Oncology, LynxDx Hana Vakil Employment: Strata Oncology Stock and Other Ownership Interests: Strata Oncology D. Bryan Johnson Employment: Strata Oncology Stock and Other Ownership Interests: Strata Oncology Daniel R. Rhodes Employment: Strata Oncology, Javelin Oncology Leadership: Strata Oncology, Javelin Oncology Stock and Other Ownership Interests: Strata Oncology, Javelin Oncology Patents, Royalties, Other Intellectual Property: I am paid royalties from the University of Michigan on license revenues related to a patent on prostate cancer gene fusions No other potential conflicts of interest were reported.
© 2021 by American Society of Clinical Oncology.
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