A large, “first-of-its-kind” trial showed that a blood test could identify cancers in women with no history of cancer and who were asymptomatic. Of about 10,000 women enrolled in the study, 134 had positive results on blood screening; 26 of these women were found to have cancers. Conventional screening after the blood test, such as mammography or colonoscopy, picked up an additional 24 cancers. These results from the landmark DETECT-A study were reported at the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting1 and published simultaneously in Science.2
The blood test (DETECT-A) is designed to be additive or complementary to standard cancer screening and was incorporated into routine medical care in this “real-world’ population without discouraging patients from undergoing other types of screening. The blood tests were performed and results were generated in labs operated by Thrive Earlier Detection Inc in collaboration with researchers at Johns Hopkins University.
The blood test detected up to 10 types of cancer, including 7 for which there is no standard diagnostic test: lymphoma, appendiceal, uterine, thyroid, kidney, ovarian, and cancer of unknown origin. Use of the blood test was not associated with unnecessary follow-up tests or invasive procedures.
“This study shows it is feasible for minimally invasive blood tests to safely detect several types of cancers in patients not previously known to have cancer.”— Nickolas Papadopoulos, PhD
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The DETECT-A study is reportedly the first time a liquid biopsy test was used clinically to screen for cancer in a population without previously detected cancer for the purposes of diagnosis and intervention, specifically treatment with an intent to cure. “This study shows it is feasible for minimally invasive blood tests to safely detect several types of cancers in patients not previously known to have cancer, enabling treatment with intent to cure in at least a subset of patients. This advance informs the design of randomized trials to establish clinical utility, cost-effectiveness, and benefit-to-risk ratio of future tests,” said presenting author Nickolas Papadopoulos, PhD, Professor of Oncology and Pathology at Johns Hopkins Medicine.
“It is encouraging that the DETECT-A study found combining standard-of-care screening with the blood test augmented the benefit of standard-of-care screening for breast, colon, and lung tumors, improving sensitivity from 47% to 71%. The sensitivity for identifying the seven other cancer types previously listed was 31%. This underscores the value of blood-based multicancer screening as both complementary and additive to standard-of-care screening,” Dr. Papadopoulos said.
The liquid biopsy blood test detects the presence of 16 cancer gene mutations in circulating DNA and the blood levels of 9 specific cancer proteins. The blood test used in the trial is an earlier version of a more advanced blood test called CancerSEEK, which currently is under study.
Participants were between the ages of 65 and 75 and had multiple comorbid conditions but were asymptomatic for cancer. Enrollees were from the Geisinger Health System of Pennsylvania and New Jersey. A positive DETECT-A test was followed by a confirmatory test. If the second test was positive, the patient underwent diagnostic positron-emission tomography/computed tomography (PET/CT) imaging. Each patient was followed for at least 12 months after testing, and all were encouraged to have routine cancer screening.
The blood test doubled the number of cancers found through screening. Of the eligible participants, 96 women developed cancers: 26 were first identified by DETECT-A; 24, by conventional imaging; and 46, by symptoms or other means. A total of 65% of the cancers (n = 17) identified by DETECT-A were local or regional, allowing for earlier intervention and 12 surgeries with an intent to cure. Among patients with the first 26 cancers identified by blood testing, 12 remain in remission and 8 remain in treatment or have stable disease approximately 9 months after diagnosis. Of the 26 cancers identified by DETECT-A, 15 patients underwent confirmatory PET-CT, and of those, 9 patients had surgery.
A 5-year follow-up is planned for all 9,911 participants, including those with positive and negative test results. According to the study authors, it may be possible that other cancers were too small to be detected by imaging or were not detected by the blood test. False-positive results leading to PET/CT occurred in 1% of cases, and 0.22% of screened patients underwent unnecessary invasive diagnostic procedures as a result of false-positive findings.
At a virtual preview for the media, this abstract was singled out as one of the highlights of the AACR Virtual Annual Meeting. It was called a “first-of-its-kind prospective study of a multicancer blood test to screen and manage 10,000 women with no history of cancer.”
Antoni Ribas, MD, PhD, Program Chair and newly inaugurated AACR President, shared his thoughts on this blood test. “This study in thousands of patients provides support for using these tests. This session will be remembered as evidence that big data support their use. We need regulatory approval for this to enter practice, but I don’t think it will be too long before we start using liquid biopsies for early detection of cancer,” he said.
Antoni Ribas, MD, PhD
Elaine Mardis, PhD
When asked whether the test would pick up cancers that would not otherwise be treated, Elaine Mardis, PhD, outgoing AACR President, said: “There is the potential for overtreatment; however, early-stage cancer types for which overtreatment is a concern (breast, prostate) are not the focus of this study. The DETECT-A study was mostly aimed at cancer types that typically we detected at advanced stages, and for which the need for early detection is most pressing,” concluded Dr. Mardis.
DISCLOSURE: Dr. Papadopoulos is a cofounder of Thrive Earlier Detection and PCGx; has equity in and serves on scientific advisory boards for NeoPhore and CagePharma; has received honoraria from Sysmex; and has received royalties from technologies licensed via Johns Hopkins University from Qiagen, Invitae, Horizon Discover, and Thermo Fisher Co. Dr. Ribas holds stock or other ownership interests in Advaxis, Arcus Biosciences, Compugen, CytomX Therapeutics, Five Prime Therapeutics, FLX Bio, ImaginAb, Lutris Pharma, Merus, Pact Pharma, Rgenix, and Tango Therapeutics; has received honoraria from Amgen, Chugai/Roche, Genentech/Roche, Merck Sharp & Dohme, Novartis, and Sanofi; has served as a consultant or advisor to Amgen, Chugai Pharma, Merck, Novartis, and Sanofi; and has received institutional research funding from Agilent and Bristol-Myers Squibb. Dr. Mardis has served as a consultant or advisor to Interpreta Inc, Kiadis Pharma, and PACT Pharma.
1. Papadopoulos N: A first-of-its-kind prospective study of a multi-cancer blood test to screen and manage 10,000 women with no history of cancer. 2020 AACR Virtual Annual Meeting. Abstract CT022. Presented April 28, 2020.
2. Lennon AM, Buchanan AD, Kinde I, et al: Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention. Science. April 28, 2020 (early release online).
Study discussant David G. Huntsman, MD, Founder and Chief Medical Officer of Contextual Genomics, noted the positive predictive value of DETECT-A was 19%, which increased to 41% with the addition of positron-emission tomography/computed tomography. He pointed out that most cancers detected by the...