A New Era of Early Cancer Detection With Blood Test May Change Cancer Screening Paradigms [ESMO Congress 2022 Press Release]

D. Schrag1, C.H. McDonnell III2, L. Nadauld3, C.A. Dilaveri4, E.A. Klein5, R. Reid6, C.R. Marinac7, K.C. Chung8, M. Lopatin9, E.T. Fung10, T.M. Beer11 
1Medical Oncology/Population Sciences, MSKCC – Memorial Sloan Kettering Cancer Center, New York, NY, USA, 2Radiology, Sutter Institute for Medical Research, Sacramento, CA, USA, 3Oncology Department, Intermountain Healthcare – Intermountain Cancer Center of St George, St. George, UT, USA, 4Internal Medicine, Mayo Clinic, Rochester, USA, 5Urology, Stanford Comprehensive Cancer Institute, Stanford, CT, USA, 6Medical Oncology, Hematology, US Oncology, Inc., Thornton, VA, USA, 7Medical Oncology/Population Sciences, Dana Farber Cancer Institute, Boston, MA, USA, 8Health Economics Outcomes Research, GRAIL LLC a subsidiary of Illumina Inc. currently held separate from Illumina Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021, Menlo Park, CA, USA, 9Biostatistics, GRAIL LLC a subsidiary of Illumina Inc. currently held separate from Illumina Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021, Menlo Park, CA, USA, 10Clinical Development, GRAIL LLC a subsidiary of Illumina Inc. currently held separate from Illumina Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021, Menlo Park, CA, USA, 11Hematology / Medical Oncology Department-Oc14p, OHSU – Center for Health & Healing Building 2, Portland, OR, USA 

Background:A validated blood-based multi-cancer early detection (MCED) test uses cfDNA and machine learning to detect a common cancer signal across >50 cancer types and predict cancer signal origin (CSO). PATHFINDER is a prospective study in a screening population that evaluated the clinical feasibility of MCED testing. 

Methods:Participants were aged ≥50 y with or without additional cancer risk factors. Blood samples were collected, cfDNA analyzed, and MCED test results returned (MCED-E, early version). Cancer status was confirmed at 1 year for all participants. The primary outcome was the extent of diagnostic testing required for resolution after cancer signal detected by MCED-E. Those with cancer signal and confirmed cancer are true positive (TP), without confirmed cancer are false positive (FP). Diagnostic evaluation was at the discretion of the treating physician. Key secondary outcomes included test performance and safety. A pre-specified analysis evaluated a refined test version (MCED-Scr) using the participants’ banked specimens without return of results. 

Results:The MCED-E test detected cancer signal in 1.4% (92/6621) of participants with analyzable samples. Cancer was confirmed in 38% (35/92). Specificity was 99.1% (6235/6290). See Table for primary and secondary outcomes. A total of 73% (24/33) of TPs had diagnostic resolution in <3 months. MCED-Scr performance was similar with MCED-E (Table). Four AEs were reported (0.06%); none were due to confirmatory diagnostic procedures. 

MCED-E 

 

TP 

FP 

Total 

 

n=35 

n=57b 

N=92 

Extent of Diagnostic Testing (Primary) 

n=33a 

n=57b 

n=90a 

>1 Imaging Test, % 

90.9 

93.0 

92.2 

>1 Invasive Procedure, % 

81.8 

29.8 

48.9 

Time to Resolution, median days (IQR) 

57 (33, 143) 

162 (44, 248) 

79 (37, 219) 

Test Performance (Secondary) 

n/N 

% (95% CI) 

PPV 

35/92 

38.0 (28.8, 48.3) 

NPV 

6235/6321 

98.6 (98.3, 98.9) 

CSO Prediction Accuracy 

33/34c 

97.1 (85.1, 99.8) 

MCED-Scr 

PPV 

25/58 

43.1 (31.2, 55.9) 

NPV 

6216/6311 

98.5 (98.2, 98.8) 

CSO Prediction Accuracy 

22/25 

88.0 (70.0, 95.8) 

aExcludes 2 TPs who had evaluation started prior to test results. bIncludes 1 participant without resolution who is conservatively assumed to be FP. c1 CSO was indeterminate. 

Conclusions: MCED testing was feasible in outpatient practice without significant AEs and with a PPV of approximately 40%. Studies to refine multi-cancer screening techniques are ongoing. 

Clinical trial identification:NCT04241796 

Editorial acknowledgement:We acknowledge Jennifer Hepker, PhD and Merrilee Johnstone, PhD (Prescott Medical Communications Group, Chicago, IL) and Neva West, PhD (NeuroWest Solutions, Seattle, WA) for medical writing, editorial, and administrative support that was funded by GRAIL LLC a subsidiary of Illumina Inc. currently held separate from Illumina Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021. 

Legal entity responsible for the study:GRAIL LLC a subsidiary of Illumina Inc. currently held separate from Illumina Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021 

Funding:GRAIL LLC a subsidiary of Illumina Inc. currently held separate from Illumina Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021

Disclosure: D. Schrag: Non-Financial Interests, Institutional, Advisory Role: GRAIL, LLC, a subsidiary of Illumina, Inc, Journal of the American Medical Association; Financial Interests, Institutional, Research Grant: GRAIL, LLC, a subsidiary of Illumina, Inc, Dana-Farber Cancer Institute; Financial Interests, Institutional, Speaker’s Bureau: Pfizer. C.H. McDonnell III: Financial Interests, Institutional, Stocks/Shares: Sutter Medical Group.  L. Nadauld: Financial Interests, Personal, Stocks/Shares: CitizenCorporation, Clarifi, Guidance Genomics. E.A. Klein: Non-Financial Interests, Institutional, Advisory Role: GRAIL, LLC, a subsidiary of Illumina, Inc, Genome Health; Financial Interests, Institutional, Research Grant: GenomeDx Biosciences. K.C. Chung: Financial Interests, Institutional, Full or part-time Employment: GRAIL, LLC, a subsidiary of Illumina, Inc. M. Lopatin: Financial Interests, Institutional, Full or part-time Employment: GRAIL, LLC, a subsidiary of Illumina, Inc. E.T. Fung: Financial Interests, Institutional, Full or part-time Employment: GRAIL, LLC, a subsidiary of Illumina, Inc.  T.M. Beer: Financial Interests, Institutional, Advisory Role: GRAIL, LLC, a subsidiary of Illumina, Inc, AbbVie, Amgen, Astellas Pharma, Astra Zeneca, Bayer, Constellation, Janssen, Myovant Sciences, Pfizer, Sanofi, Sapience Therapeutics, Bristol-Meyers Squib, Clovis Oncology, Dantari Pharmaceuticals, GlaxoSmithKline, Novartis, Tolero; Financial Interests, Personal and Institutional, Stocks/Shares: Arvinas, Inc; Financial Interests, Personal, Stocks/Shares: Salarius Pharmaceuticals, LLC; Other, Institutional, Research Grant, Grant paid to Institution: Alliance Foundation Trials, Astellas Pharma, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Endocyte Inc., Exact Sciences Corp., Freenome, GRAIL, LLC, a subsidiary of Illumina, Inc, Harpoon Therapeutics, Janssen Research & Development, Medivation, Inc., Merck, Sotio, Theraclone Sciences/OncoResponse, Zenith Epigenetics. All other authors have declared no conflicts of interest. 

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