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CHICAGO – according to the first interim report from a substudy of the large, ongoing Circulating Cell-free Genome Atlas (CCGA).
“Lung cancer screening with low-dose CT is known to improve outcomes. And yet, CT-based lung cancer screening is not widely adopted,” said lead study author Geoffrey R. Oxnard, MD, associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, Boston, in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the study was reported. “Criticisms of low-dose CT include the risk of false positives and overdiagnosis. We proposed to investigate an untapped opportunity for cancer detection, which is using cell-free DNA.”
Main substudy results among 164 patients with lung cancer and 923 comparable individuals without known cancer showed that at a specificity of 98%, the three assays evaluated detected up to 51% of early-stage (stage I-IIIA) lung cancers and up to 91% of late-stage (stage IIIB-IV) lung cancers. And among the healthy participants with false-positive results for lung cancer, several were ultimately found to have cancers of other types.
“This first interim analysis of the CCGA study demonstrates that comprehensive sequencing of the plasma cell-free DNA can generate high-quality data across the entire genome, and it permits noninvasive cancer detection. The assays can detect lung cancer across stages, across histologies, across populations,” Dr. Oxnard said.
“Together, these results support the promise of using cell-free, DNA-based assays to develop an early cancer detection test with high specificity. Further assay and clinical development is ongoing: There is a separate prospective trial enrolling, the STRIVE study, and there remain thousands of patients still on this CCGA study to be analyzed for further optimization and focusing of this assay towards an eventual cancer diagnostic.”
The cohort studied was not a screening population, so the assays’ performance cannot be compared with that of low-dose CT at this point, he said. But the hypothesis going forward is that the assays will have comparatively higher specificity, sparing some patients an unnecessary diagnostic work-up.
The population in which the final blood test might be used will depend on its diagnostic performance once the assays are fully refined and clinic ready, which will take some time, according to Dr. Oxnard. However, “2 years ago, this was a pipe dream. Two years ago, it was completely just a brainstorm that had no data to support it, and I didn’t believe that this could be done. Today, we actually have data to show that this is really feasible to find early-stage cancer in the blood. So this is a huge step forward and actually means that this is going to be a reality.”
“This is an important first step towards an easier way to detect lung cancer at earlier and hopefully more curable stages,” agreed ASCO Expert David Graham, MD, who is also medical director at the Levine Cancer Institute in Charlotte, N.C. “If the promise of this report holds, we could easily see a day when a person could be screened for lung cancer and possibly other cancers simply by going into their regular doctor’s office for a blood draw.”
Study details
The CCGA study has enrolled more than 12,000 of its planned 15,000 participants (70% with cancer, 30% without) across 142 U.S. and Canadian sites.
The substudy reported had a development cohort (118 patients with lung cancer, 561 individuals without cancer) and a validation cohort (46 patients with lung cancer, 362 individuals without cancer), with the lung cancer and noncancer groups matched on age, race, and body mass index. “Having a comparable control cohort is very important in developing such a diagnostic for accurate analysis of the potential false-positive rate,” Dr. Oxnard noted.
Three prototype assays were tested: A targeted sequencing assay entailing very deep sequencing across 507 genes for somatic mutations such as single-nucleotide variants and small insertions and/or deletions; a novel, whole-genome sequencing assay to detect somatic gene copy number changes; and a novel, whole-genome methylation sequencing assay to detect abnormal epigenetic changes.
Sequencing was also performed on DNA from white blood cells. “That’s very important. The white blood cells are rich with mutations that can pollute the DNA and make you think that there is cancer present in the cell-free DNA,” Dr. Oxnard explained. “You screen out this interference from the white blood cells and other biologic noise, and you are left with the final features: mutations, copy number variations, and methylation signatures that then go into the final assays being studied.”
Results showed that when assay specificity was 98%, sensitivity for early-stage (stage I-IIIA) lung cancer ranged from 38% to 51%, and sensitivity for late-stage (stage IIIB-IV) lung cancer ranged from 87% to 91%.
Among five presumed cancer-free individuals having positive results on all three assays, two subsequently received a cancer diagnosis (one with stage III ovarian cancer, one with stage II endometrial cancer).
An additional 19 cancer types across all stages were tested in the CCGA substudy. Early results for breast, gastrointestinal, gynecologic, blood, and other cancers were also reported at the meeting (abstracts 536, 12021, and 12003).
Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.
SOURCE: Oxnard GR et al. ASCO 2018. Abstract LBA8501.
CHICAGO – according to the first interim report from a substudy of the large, ongoing Circulating Cell-free Genome Atlas (CCGA).
“Lung cancer screening with low-dose CT is known to improve outcomes. And yet, CT-based lung cancer screening is not widely adopted,” said lead study author Geoffrey R. Oxnard, MD, associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, Boston, in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the study was reported. “Criticisms of low-dose CT include the risk of false positives and overdiagnosis. We proposed to investigate an untapped opportunity for cancer detection, which is using cell-free DNA.”
Main substudy results among 164 patients with lung cancer and 923 comparable individuals without known cancer showed that at a specificity of 98%, the three assays evaluated detected up to 51% of early-stage (stage I-IIIA) lung cancers and up to 91% of late-stage (stage IIIB-IV) lung cancers. And among the healthy participants with false-positive results for lung cancer, several were ultimately found to have cancers of other types.
“This first interim analysis of the CCGA study demonstrates that comprehensive sequencing of the plasma cell-free DNA can generate high-quality data across the entire genome, and it permits noninvasive cancer detection. The assays can detect lung cancer across stages, across histologies, across populations,” Dr. Oxnard said.
“Together, these results support the promise of using cell-free, DNA-based assays to develop an early cancer detection test with high specificity. Further assay and clinical development is ongoing: There is a separate prospective trial enrolling, the STRIVE study, and there remain thousands of patients still on this CCGA study to be analyzed for further optimization and focusing of this assay towards an eventual cancer diagnostic.”
The cohort studied was not a screening population, so the assays’ performance cannot be compared with that of low-dose CT at this point, he said. But the hypothesis going forward is that the assays will have comparatively higher specificity, sparing some patients an unnecessary diagnostic work-up.
The population in which the final blood test might be used will depend on its diagnostic performance once the assays are fully refined and clinic ready, which will take some time, according to Dr. Oxnard. However, “2 years ago, this was a pipe dream. Two years ago, it was completely just a brainstorm that had no data to support it, and I didn’t believe that this could be done. Today, we actually have data to show that this is really feasible to find early-stage cancer in the blood. So this is a huge step forward and actually means that this is going to be a reality.”
“This is an important first step towards an easier way to detect lung cancer at earlier and hopefully more curable stages,” agreed ASCO Expert David Graham, MD, who is also medical director at the Levine Cancer Institute in Charlotte, N.C. “If the promise of this report holds, we could easily see a day when a person could be screened for lung cancer and possibly other cancers simply by going into their regular doctor’s office for a blood draw.”
Study details
The CCGA study has enrolled more than 12,000 of its planned 15,000 participants (70% with cancer, 30% without) across 142 U.S. and Canadian sites.
The substudy reported had a development cohort (118 patients with lung cancer, 561 individuals without cancer) and a validation cohort (46 patients with lung cancer, 362 individuals without cancer), with the lung cancer and noncancer groups matched on age, race, and body mass index. “Having a comparable control cohort is very important in developing such a diagnostic for accurate analysis of the potential false-positive rate,” Dr. Oxnard noted.
Three prototype assays were tested: A targeted sequencing assay entailing very deep sequencing across 507 genes for somatic mutations such as single-nucleotide variants and small insertions and/or deletions; a novel, whole-genome sequencing assay to detect somatic gene copy number changes; and a novel, whole-genome methylation sequencing assay to detect abnormal epigenetic changes.
Sequencing was also performed on DNA from white blood cells. “That’s very important. The white blood cells are rich with mutations that can pollute the DNA and make you think that there is cancer present in the cell-free DNA,” Dr. Oxnard explained. “You screen out this interference from the white blood cells and other biologic noise, and you are left with the final features: mutations, copy number variations, and methylation signatures that then go into the final assays being studied.”
Results showed that when assay specificity was 98%, sensitivity for early-stage (stage I-IIIA) lung cancer ranged from 38% to 51%, and sensitivity for late-stage (stage IIIB-IV) lung cancer ranged from 87% to 91%.
Among five presumed cancer-free individuals having positive results on all three assays, two subsequently received a cancer diagnosis (one with stage III ovarian cancer, one with stage II endometrial cancer).
An additional 19 cancer types across all stages were tested in the CCGA substudy. Early results for breast, gastrointestinal, gynecologic, blood, and other cancers were also reported at the meeting (abstracts 536, 12021, and 12003).
Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.
SOURCE: Oxnard GR et al. ASCO 2018. Abstract LBA8501.
CHICAGO – according to the first interim report from a substudy of the large, ongoing Circulating Cell-free Genome Atlas (CCGA).
“Lung cancer screening with low-dose CT is known to improve outcomes. And yet, CT-based lung cancer screening is not widely adopted,” said lead study author Geoffrey R. Oxnard, MD, associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, Boston, in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the study was reported. “Criticisms of low-dose CT include the risk of false positives and overdiagnosis. We proposed to investigate an untapped opportunity for cancer detection, which is using cell-free DNA.”
Main substudy results among 164 patients with lung cancer and 923 comparable individuals without known cancer showed that at a specificity of 98%, the three assays evaluated detected up to 51% of early-stage (stage I-IIIA) lung cancers and up to 91% of late-stage (stage IIIB-IV) lung cancers. And among the healthy participants with false-positive results for lung cancer, several were ultimately found to have cancers of other types.
“This first interim analysis of the CCGA study demonstrates that comprehensive sequencing of the plasma cell-free DNA can generate high-quality data across the entire genome, and it permits noninvasive cancer detection. The assays can detect lung cancer across stages, across histologies, across populations,” Dr. Oxnard said.
“Together, these results support the promise of using cell-free, DNA-based assays to develop an early cancer detection test with high specificity. Further assay and clinical development is ongoing: There is a separate prospective trial enrolling, the STRIVE study, and there remain thousands of patients still on this CCGA study to be analyzed for further optimization and focusing of this assay towards an eventual cancer diagnostic.”
The cohort studied was not a screening population, so the assays’ performance cannot be compared with that of low-dose CT at this point, he said. But the hypothesis going forward is that the assays will have comparatively higher specificity, sparing some patients an unnecessary diagnostic work-up.
The population in which the final blood test might be used will depend on its diagnostic performance once the assays are fully refined and clinic ready, which will take some time, according to Dr. Oxnard. However, “2 years ago, this was a pipe dream. Two years ago, it was completely just a brainstorm that had no data to support it, and I didn’t believe that this could be done. Today, we actually have data to show that this is really feasible to find early-stage cancer in the blood. So this is a huge step forward and actually means that this is going to be a reality.”
“This is an important first step towards an easier way to detect lung cancer at earlier and hopefully more curable stages,” agreed ASCO Expert David Graham, MD, who is also medical director at the Levine Cancer Institute in Charlotte, N.C. “If the promise of this report holds, we could easily see a day when a person could be screened for lung cancer and possibly other cancers simply by going into their regular doctor’s office for a blood draw.”
Study details
The CCGA study has enrolled more than 12,000 of its planned 15,000 participants (70% with cancer, 30% without) across 142 U.S. and Canadian sites.
The substudy reported had a development cohort (118 patients with lung cancer, 561 individuals without cancer) and a validation cohort (46 patients with lung cancer, 362 individuals without cancer), with the lung cancer and noncancer groups matched on age, race, and body mass index. “Having a comparable control cohort is very important in developing such a diagnostic for accurate analysis of the potential false-positive rate,” Dr. Oxnard noted.
Three prototype assays were tested: A targeted sequencing assay entailing very deep sequencing across 507 genes for somatic mutations such as single-nucleotide variants and small insertions and/or deletions; a novel, whole-genome sequencing assay to detect somatic gene copy number changes; and a novel, whole-genome methylation sequencing assay to detect abnormal epigenetic changes.
Sequencing was also performed on DNA from white blood cells. “That’s very important. The white blood cells are rich with mutations that can pollute the DNA and make you think that there is cancer present in the cell-free DNA,” Dr. Oxnard explained. “You screen out this interference from the white blood cells and other biologic noise, and you are left with the final features: mutations, copy number variations, and methylation signatures that then go into the final assays being studied.”
Results showed that when assay specificity was 98%, sensitivity for early-stage (stage I-IIIA) lung cancer ranged from 38% to 51%, and sensitivity for late-stage (stage IIIB-IV) lung cancer ranged from 87% to 91%.
Among five presumed cancer-free individuals having positive results on all three assays, two subsequently received a cancer diagnosis (one with stage III ovarian cancer, one with stage II endometrial cancer).
An additional 19 cancer types across all stages were tested in the CCGA substudy. Early results for breast, gastrointestinal, gynecologic, blood, and other cancers were also reported at the meeting (abstracts 536, 12021, and 12003).
Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.
SOURCE: Oxnard GR et al. ASCO 2018. Abstract LBA8501.
REPORTING FROM ASCO 2018
Key clinical point: Three blood-based assays performed moderately well for identifying lung cancer in early, potentially curable stages.
Major finding: At 98% specificity, the assays had sensitivities of 38%-51% for detecting lung cancers of stage I-IIIA.
Study details: A case-control study of circulating cell-free DNA assays among 164 patients with lung cancer and 923 comparable individuals without cancer.
Disclosures: Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.
Source: Oxnard GR et al. ASCO 2018. Abstract LBA8501.