A minimally invasive blood test has been found to be feasible to safely detect several types of cancers in patients without a history of malignancies.
A minimally invasive blood test has been found to be feasible to safely detect several types of cancers in patients without a history of malignancies, enabling treatment with curative intent in a subset of individuals, according to real-world results of an interim analysis of the DETECT-A study presented at the 2020 AACR Virtual Annual Meeting.1
Findings showed that the addition of the plasma assay to imaging more than doubled the number of cancers initially detected by current standard-of-care tests, from 25% to 52%. The blood test was also able to identify 10 different tumor types, 7 of which currently have no standard-of-care screening assays available. Furthermore, 65% of the cancers detected via the blood test were classified as local or regional disease.
When used in combination with standard PET-CT imaging, the blood test minimized false positive results with 99.6% specificity. When used alone, screening with the blood test had a 98.9% specificity. Moreover, the use of the blood test plus imaging led to a positive predictive value of 40.6%.
“It is feasible for a minimally invasive blood test to safely detect several types of cancers in individuals without known cancer leading to treatment with intent to cure,” said lead study author Nick Papadopoulos, PhD, professor of oncology and pathology at Johns Hopkins School of Medicine, in a virtual presentation during the meeting. “In a subset of them, it is important that the blood test identifies screen-detected cancers in addition to those identified by the standard-of-care screening. This advance informs the design of randomized trials to establish clinical utility, cost effectiveness, and benefit-to-risk ratio of future tests.”
Earlier detection is necessary to improve the statistics of curative treatment. Fifty-eight percent of patients present with metastatic disease, with a 5-year overall survival (OS) rate of 30%, according to SEER data. Twenty-one percent of cases have regional disease, which has a 5-year OS rate of 75%. For localized disease, which comprises 16% of all cases, the 5-year OS rate is 93%.
However, current standard-of-care screening tests, such as mammography and colonoscopy, detect less than 30% of all incident cancers.
The multi-cancer, multi-analyte screening blood test, which is an earlier version of CancerSEEK that was developed in 2016 by Thrive, incorporates DNA and protein markers. Additionally, it comprises 1933 bases covering regions of 16 commonly mutated genes and 9 proteins that are known to be linked with cancer. Investigators hypothesized that when combined with standard screening, the blood test would allow for a doubling number of cancers detected by screening.
In the prospective, interventional DETECT-A study, which stands for Detecting cancers Earlier Through Elective mutation-based blood Collection and Testing, investigators sought to: determine whether the multi-cancer plasma assay can prospectively detect cancer in those whose cancers were not previously detected by other forms; whether the test can be used to intervene in the disease progression process to lead to a treatment with curative intent; whether the assay can be incorporated into routine clinical care and discourage individuals from standard-of-care screening; and whether such an assay is safe and does not lead to invasive follow-up tests.
In the study design, the blood test was reviewed by a multidisciplinary committee, followed by imaging via PET-CT of individuals who had positive tests, who were then followed up.
Investigators enrolled 10,006 women between September 2017 and May 2019 who were between the ages of 65 and 75 years with no prior history of cancer; the population was also of one with a high degree of compliance with standard-of-care screening.
Patients were screened with the blood test. Those with positive results were then followed by an imaging test, which often consisted of a PET-CT scan, in order to localize the supposed malignancy.
In the analysis, among the eligible participants, 96 women developed cancers: 26 of these were first identified by the blood test, 24 were first identified by standard-of-care screening methods, and 46 women were first identified by symptoms or other means. The blood test’s sensitivity was 27.1% across all cancers and 31.1% for the 7 cancers that have no screening options. The combination of the plasma test and imaging had a combined sensitivity of 52.1%, suggesting that the assay is an added benefit and is complementary to standard-of-care screening tools.
Furthermore, the addition of the blood test did not discourage standard screening methods for those who participated in the trial. Moreover, TP53, BRAF, KRAS, or PIK3CA were the most common abnormalities that were identified via plasma. Additionally, in cases for which tumor tissue was also available, the plasma-detected mutations were also confirmed to be present in the primary tumor.
Regarding safety, no serious adverse events were observed on the study. Three surgeries were performed in individuals whose tests were positive but did not have cancer. These procedures were for large colonic polyps with high-grade dysplasia, which could not be removed endoscopically; in situ carcinoma of the appendix; and a 10-cm ovarian lesion that was later determined to be mucinous cystadenoma.
“This study is a seminal moment in cancer screening that advances the entire field,” Christoph Lengauer, PhD, co-founder and chief innovation officer of Thrive, stated in a press release.2 “For the first time, a blood test was utilized in a real-world setting and was able to more than double the number of cancers first identified through screening methods. We learned that it can be both complementary to existing standard-of-care screening tools, and a significant benefit for many types of cancers like ovarian, appendix, and kidney, which do not have any current screening modalities.”
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. Presented at: 2020 AACR Virtual Annual Meeting I; April 27-28, 2020. Abstract CT031.
2. Thrive earlier detection announces groundbreaking clinical data from the first ever interventional study of a blood-based test to screen and identify multiple types of cancer [news release]: Thrive; April 28, 2020. bit.ly/3bY7lK4. Accessed April 28, 2020.