A New Era of Early Cancer Detection With Blood Test

New tests can detect common cancer signal across over 50 types of cancer from tumour DNA in blood
Latest results are an important first step to early detection of previously hard to find cancers
Cancer services must step up to redefine early cancer detection and the provision of care

Date: 11 Sep 2022

Topics:

Basic Science; Cancer Diagnostics; Clinical Research; Targeted Therapy

PARIS, France - Cancer doctors, care providers and payers need to get ready for a major shift in early cancer detection that will affect almost every stage of cancer diagnosis and treatment. New data supporting the accuracy of multi-cancer early detection (MCED) blood testing (1), presented at the ESMO Congress 2022, have major implications for future cancer care provision, said Fabrice André, ESMO 2022 Scientific Co-Chair.

“It is a duty of professional societies like ESMO to raise awareness of the fact that within the next five years, we will need more doctors, surgeons and nurses, together with more diagnostic and treatment infrastructure, to care for the rising number of people who will be identified by multi-cancer early detection tests,” explained André, Director of Research at Gustave Roussy Cancer Centre, Villejuif, France and newly elected future president of the Society for the years 2025-2026. “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests, for example in the diagnosis and treatment of people with pancreatic and other cancers that are usually diagnosed at a much later stage.”

New MCED tests in development can detect a common cancer signal from over 50 different types of cancer and predict where the signal has come from in the body. The signal arises from small sequences of circulating tumour DNA (ctDNA) in the blood which have some different methylation patterns from non-tumour DNA.

In the PATHFINDER study reported at the ESMO Congress 2022, an MCED test detected a cancer signal in 1.4% of 6621 people aged 50 years and over who were not known to have cancer, and cancer was confirmed in 38% of those with a positive test. Of 6290 people who were cancer free, 99.1% received a negative test result. Among those with a positive test result, the time to achieve diagnostic resolution (i.e. to find cancer or decide there was no evidence of malignancy requiring further investigation) was a median of 79 days. Among participants with a positive screening test, diagnostic resolution was achieved within three months for 73%.

“The results are an important first step for early cancer detection tests because they showed a good detection rate for people who had cancer and an excellent specificity rate for those who did not have cancer. In people with a positive test, it took less than two months to confirm the diagnosis if they had cancer and it took a bit longer if they did not have cancer primarily because physicians opted to perform imaging studies and then repeat them a second time several months later to investigate the possibility of a cancer diagnosis,” explained study senior author Deb Schrag, Memorial Sloan Kettering Cancer Center, New York, USA.

“An important finding was that few participants with a false positive screening test required multiple invasive procedures such as endoscopies and biopsies. This finding should help to allay concerns that these tests could cause harm by generating unnecessary procedures in people who are well,” added Schrag.

She stressed the importance of continued standard screening for tumours, such as breast and colorectal cancer, while MCED tests are being refined and validated for cancers such as pancreatic, small bowel and stomach cancer where there are currently no screening options.

“This study indicates that hope is on the horizon for detecting cancers that are currently unscreenable, but of course much more work is needed and, with experience and larger samples, these assays will improve. The tests need to be refined so they are better at distinguishing tumour DNA from all the other DNA that is circulating in the blood,” said Schrag. “It is also critical to note that the purpose of cancer screening is not to decrease the incidence of cancer, but rather to decrease cancer mortality. It is premature to reach any conclusions about how MCED testing affects mortality which was not measured in the PATHFINDER study and requires lengthy follow-up.”

The study reported at the ESMO Congress 2022 is the first prospective investigation to show that an MCED test can detect cancer in patients with undiagnosed cancer, as previous studies used tests only in patients already known to have cancer. A number of further studies are now underway including a major randomised clinical trial enrolling 140,000 asymptomatic people in England to investigate the clinical effectiveness of MCED testing on cancer outcomes (2).

“We need comparative trials across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” said André. “In addition, we need to know more about the small proportion of false positive tests – MCED results that indicate cancer is present but this is not confirmed by standard diagnostic procedures. We need some of these answers before we can calculate the cost impact of introducing MCED tests in routine clinical practice,” André concluded.

Disclaimer

This press release contains information provided by the author of the highlighted abstract and reflects the content of this abstract. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct.

References

Abstract 903O ‘A prospective study of a multi-cancer early detection blood test’ will be presented by Deb Schrag during the proffered paper session “Basic science and translational research” on Sunday, 11 September, 16:30 to 18:00 CEST in Orléans Auditorium. Annals of Oncology, Volume 33 Supplement 7, September 2022
Swanton C, Neal RD, Johnson PWM et al. NHS-Galleri Trial Design: Equitable study recruitment tactics for targeted population-level screening with a multi-cancer early detection (MCED) test. J Clin Oncol 2022; 40(16) suppl.

903O - A prospective study of a multi-cancer early detection blood test

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=57^b	N=92
Extent of Diagnostic Testing (Primary)	n=33^a	n=57^b	n=90^a
>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	33/34^c	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.