Abstract 908P
Background
A multi-cancer early detection (MCED) test using methylation patterns in plasma cell-free DNA to detect a cancer signal and predict site of origin was evaluated in the prospective PATHFINDER study. Because MCED testing has the potential to cause anxiety and distress, participant-reported outcomes were assessed.
Methods
Adults ≥50 y with or without additional cancer risk factors (a cancer diagnosis >3 years prior, smoking history, genetic predisposition) underwent the MCED blood test to screen for cancer. When a cancer signal was detected, the diagnostic workup was directed by the physician. Participants completed the Patient Reported Outcomes Measurement Information System (PROMIS) anxiety short form (higher scores = increased anxiety) pre-MCED test, post return of MCED test results (RoR), diagnostic resolution, and at end of study (EOS; 12 months). An adapted Multidimensional Impact of Cancer Risk Assessment (MICRA, higher scores = worsening) was completed post RoR. A three-item satisfaction questionnaire was completed post RoR for those with a signal not detected or at diagnostic resolution for signal detected.
Results
Participants with a cancer signal detected had increased anxiety following RoR which decreased by EOS (Table). MICRA scores were low, though participants with cancer signal detected had greater distress and uncertainty and worse experience vs those with no signal detected (Table). Of the 89.4% of participants who completed the satisfaction questionnaire, most were satisfied with the test (n=5749/5920; 48.5% extremely satisfied, 33.3% very satisfied, 15.3% satisfied) regardless of the MCED test result or cancer status upon diagnostic resolution. Table: 908P
| Scale (score range) completion rate n/N, % | Signal detected mean (SD) | No signal detected mean (SD) |
| PROMIS anxiety (0-100), Pre test 6434/6621, 97.2% | n=88 47.0 (7.1) | n=6346 47.6 (7.5) |
| Δ Post test at RoR 5789/6621, 87.4% | 3.6 (7.2) | 0.7 (6.4) |
| Δ Diagnostic resolution 58/91, 63.7% | 2.5 (6.3) | — |
| True Positive | 4.7 (6.1) | — |
| False Positive | 0.8 (6.1) | — |
| Δ End of study 5310/6621, 80.2% | 0.6 (7.2) | 0.7 (7.1) |
| True positive | 1.2 (6.4) | — |
| False positive | 0.1 (7.8) | — |
| MICRA, Total score (0-95) 5914/6621, 89.3% | n=50 28.4 (14.9) | n=5864 8.8 (7.2) |
| Distress (0-30) | 7.6 (6.9) | 0.6 (1.8) |
| Uncertainty (0-45) | 11.3 (7.4) | 3.2 (4.2) |
| Positive experience (0-20, higher score = worse experience) | 9.6 (4.6) | 5.0 (5.5) |
Conclusions
While anxiety was elevated following a positive MCED test result, it was more pronounced for participants diagnosed with cancer, and did approach baseline by EOS for both true and false positive participants. High rates of satisfaction were reported with MCED testing irrespective of test result.
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, Personal, Other, Research Agreements: Dana-Farber Cancer Institute; Non-Financial Interests, Personal, Licensing Fees: Dana-Farber Cancer Institute; Financial Interests, Personal, Other, Sponsored Travel: Dana-Farber Cancer Institute; Financial Interests, Personal, Other, Consulting: JAMA; Financial Interests, Personal, Advisory Role: University of North Carolina; Non-Financial Interests, Personal, Advisory Role: 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. T.M. Beer: Non-Financial Interests, Institutional, Advisory Role: 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, Arvinas; Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, Astellas Pharma, AstraZeneca, Bayer, Constellation, Janssen, Myovant Sciences, Pfizer, Sanofi, Sapience Therapeutics, Bristol Myers Squibb, Clovis, Dantari Pharmaceuticals, GlaxoSmithKline, Novartis, Tolero; Financial Interests, Personal and Institutional, Stocks/Shares: Arnivas; Financial Interests, Personal, Stocks/Shares: Salarius Pharmaceuticals; Other, Institutional, Research Grant, Grant paid to institution: AllianceFoundation, Astellas Pharma, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Endocyte Inc., Exact Sciences Corp, Freenome, 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, Harpoon Therapeutics, Janssen Research and Development, Medivation, Merck, Sotio, Theraclone Sciences/On, Zenith Epigenetics. C.H. McDonnell III: Financial Interests, Personal and Institutional, Stocks/Shares: Sutter Medical Group. L. Nadauld: Financial Interests, Personal, Stocks/Shares: Citizen Corporation, Clarifi, Guidance Genomics. E.A. Klein: Non-Financial Interests, Institutional, Advisory Role: 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, Genome Health, GenomeDx Biosciences; 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. currently held separate from Illumina Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021. M. Lopatin: Financial Interests, Institutional, Full or part-time Employment: 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. E.T. Fung: Financial Interests, Institutional, Full or part-time Employment: 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. D.L. Patrick: Financial Interests, Institutional, Advisory Role: 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. All other authors have declared no conflicts of interest.