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American Society of Clinical Oncology (ASCO)/ European Organisation for Research and Treatment of Cancer (EORTC)/ National Cancer Institute (NCI): Markers in Cancer
Gene panel identifies residual neuroblastoma metastases
BRUSSELS – In advanced-stage neuroblastoma patients with residual metastases in their bone marrow following two cycles of anti-GD2 immunotherapy, another cycle of this treatment is futile and only causes adverse events, based on a review of 343 stage IV patients treated at one U.S. center.
"Bone marrow minimal residual disease [MRD] measured after two cycles of immunotherapy was the strongest predictor of outcome, irrespective of disease status at the start of immunotherapy," Dr. Nai-Kong V. Cheung said at the Markers in Cancer meeting. "If a patient is positive for MRD after two cycles, don’t continue the treatment."
In the series of 343 patients aged 18 months or older with metastatic, stage IV neuroblastoma that he reviewed, all patients with detectable MRD after two cycles of immunotherapy with GD2 antibody eventually relapsed or died within the next 5 years. In contrast, roughly half of the patients who lacked MRD after the first two cycles of anti-GD2 therapy remained progression free and alive during up to 20 years of follow-up.
The full course of anti-GD2 treatment takes 2 years, has the potential to cause adverse effects, and is painful and expensive. "Why continue and subject patients to a treatment that won’t be beneficial?" Dr. Cheung asked during an interview. "We can use [MRD] as a marker to take patients off of a protocol that will not be useful to them and try a different treatment."
Immunotherapy with anti-GD2 is part of standard treatment for patients with advanced neuroblastoma.
Dr. Cheung, a pediatric oncologist and head of the neuroblastoma program at Memorial Sloan-Kettering Cancer Center in New York, and his associates used a four-marker genetic analysis to find evidence of residual, metastatic neuroblastoma cells in patients’ bone marrow. The four markers they used were:
• GD2 synthase, the gene for an enzyme that helps produce a ganglioside-abundant in neuroblastoma cells;
• PHOX2B, the gene for a transcription factor that promotes nerve cell growth and maturation;
• CCND1, the gene for cyclin D1 protein, an oncogene; and
• ISL 1, the gene for islet 1, a transcription factor involved in cell growth.
The database included 169 patients treated during first remission, 69 treated during second or later remission, and 105 with primary refractory disease. The researchers used the four-test genetic panel to screen for MRD in bone marrow specimens taken from these patients after the first two rounds of anti-GD2 treatment with or without granulocyte-macrophage colony-stimulating factor in a series of four treatment protocols. A patient was considered positive for MRD if at least one of the genetic markers was positive for the presence of neuroblastoma cells in the bone marrow.
In a multivariate analysis, patients negative for MRD had about a fourfold increased rate of progression-free survival and about a threefold increased rate of overall survival, compared with patients positive for MRD; both differences were statistically significant.
Dr. Cheung said that the four-gene panel his group used was developed through a project begun 15 years ago to look for the most discriminating gene signatures of metastatic neuroblastoma cells against the background of normal bone marrow cells, the metastatic destination for at least 90% of advanced neuroblastoma tumors. A similar approach could identify genetic tests for treatment response of other metastatic tumor types, he said.
The meeting was sponsored by the American Society of Clinical Oncology, the European Organisation for Research and Treatment of Cancer, and the National Cancer Institute. Dr. Cheung said that he is a coinventor on patents held by Memorial Sloan-Kettering Cancer Center.
On Twitter @mitchelzoler
BRUSSELS – In advanced-stage neuroblastoma patients with residual metastases in their bone marrow following two cycles of anti-GD2 immunotherapy, another cycle of this treatment is futile and only causes adverse events, based on a review of 343 stage IV patients treated at one U.S. center.
"Bone marrow minimal residual disease [MRD] measured after two cycles of immunotherapy was the strongest predictor of outcome, irrespective of disease status at the start of immunotherapy," Dr. Nai-Kong V. Cheung said at the Markers in Cancer meeting. "If a patient is positive for MRD after two cycles, don’t continue the treatment."
In the series of 343 patients aged 18 months or older with metastatic, stage IV neuroblastoma that he reviewed, all patients with detectable MRD after two cycles of immunotherapy with GD2 antibody eventually relapsed or died within the next 5 years. In contrast, roughly half of the patients who lacked MRD after the first two cycles of anti-GD2 therapy remained progression free and alive during up to 20 years of follow-up.
The full course of anti-GD2 treatment takes 2 years, has the potential to cause adverse effects, and is painful and expensive. "Why continue and subject patients to a treatment that won’t be beneficial?" Dr. Cheung asked during an interview. "We can use [MRD] as a marker to take patients off of a protocol that will not be useful to them and try a different treatment."
Immunotherapy with anti-GD2 is part of standard treatment for patients with advanced neuroblastoma.
Dr. Cheung, a pediatric oncologist and head of the neuroblastoma program at Memorial Sloan-Kettering Cancer Center in New York, and his associates used a four-marker genetic analysis to find evidence of residual, metastatic neuroblastoma cells in patients’ bone marrow. The four markers they used were:
• GD2 synthase, the gene for an enzyme that helps produce a ganglioside-abundant in neuroblastoma cells;
• PHOX2B, the gene for a transcription factor that promotes nerve cell growth and maturation;
• CCND1, the gene for cyclin D1 protein, an oncogene; and
• ISL 1, the gene for islet 1, a transcription factor involved in cell growth.
The database included 169 patients treated during first remission, 69 treated during second or later remission, and 105 with primary refractory disease. The researchers used the four-test genetic panel to screen for MRD in bone marrow specimens taken from these patients after the first two rounds of anti-GD2 treatment with or without granulocyte-macrophage colony-stimulating factor in a series of four treatment protocols. A patient was considered positive for MRD if at least one of the genetic markers was positive for the presence of neuroblastoma cells in the bone marrow.
In a multivariate analysis, patients negative for MRD had about a fourfold increased rate of progression-free survival and about a threefold increased rate of overall survival, compared with patients positive for MRD; both differences were statistically significant.
Dr. Cheung said that the four-gene panel his group used was developed through a project begun 15 years ago to look for the most discriminating gene signatures of metastatic neuroblastoma cells against the background of normal bone marrow cells, the metastatic destination for at least 90% of advanced neuroblastoma tumors. A similar approach could identify genetic tests for treatment response of other metastatic tumor types, he said.
The meeting was sponsored by the American Society of Clinical Oncology, the European Organisation for Research and Treatment of Cancer, and the National Cancer Institute. Dr. Cheung said that he is a coinventor on patents held by Memorial Sloan-Kettering Cancer Center.
On Twitter @mitchelzoler
BRUSSELS – In advanced-stage neuroblastoma patients with residual metastases in their bone marrow following two cycles of anti-GD2 immunotherapy, another cycle of this treatment is futile and only causes adverse events, based on a review of 343 stage IV patients treated at one U.S. center.
"Bone marrow minimal residual disease [MRD] measured after two cycles of immunotherapy was the strongest predictor of outcome, irrespective of disease status at the start of immunotherapy," Dr. Nai-Kong V. Cheung said at the Markers in Cancer meeting. "If a patient is positive for MRD after two cycles, don’t continue the treatment."
In the series of 343 patients aged 18 months or older with metastatic, stage IV neuroblastoma that he reviewed, all patients with detectable MRD after two cycles of immunotherapy with GD2 antibody eventually relapsed or died within the next 5 years. In contrast, roughly half of the patients who lacked MRD after the first two cycles of anti-GD2 therapy remained progression free and alive during up to 20 years of follow-up.
The full course of anti-GD2 treatment takes 2 years, has the potential to cause adverse effects, and is painful and expensive. "Why continue and subject patients to a treatment that won’t be beneficial?" Dr. Cheung asked during an interview. "We can use [MRD] as a marker to take patients off of a protocol that will not be useful to them and try a different treatment."
Immunotherapy with anti-GD2 is part of standard treatment for patients with advanced neuroblastoma.
Dr. Cheung, a pediatric oncologist and head of the neuroblastoma program at Memorial Sloan-Kettering Cancer Center in New York, and his associates used a four-marker genetic analysis to find evidence of residual, metastatic neuroblastoma cells in patients’ bone marrow. The four markers they used were:
• GD2 synthase, the gene for an enzyme that helps produce a ganglioside-abundant in neuroblastoma cells;
• PHOX2B, the gene for a transcription factor that promotes nerve cell growth and maturation;
• CCND1, the gene for cyclin D1 protein, an oncogene; and
• ISL 1, the gene for islet 1, a transcription factor involved in cell growth.
The database included 169 patients treated during first remission, 69 treated during second or later remission, and 105 with primary refractory disease. The researchers used the four-test genetic panel to screen for MRD in bone marrow specimens taken from these patients after the first two rounds of anti-GD2 treatment with or without granulocyte-macrophage colony-stimulating factor in a series of four treatment protocols. A patient was considered positive for MRD if at least one of the genetic markers was positive for the presence of neuroblastoma cells in the bone marrow.
In a multivariate analysis, patients negative for MRD had about a fourfold increased rate of progression-free survival and about a threefold increased rate of overall survival, compared with patients positive for MRD; both differences were statistically significant.
Dr. Cheung said that the four-gene panel his group used was developed through a project begun 15 years ago to look for the most discriminating gene signatures of metastatic neuroblastoma cells against the background of normal bone marrow cells, the metastatic destination for at least 90% of advanced neuroblastoma tumors. A similar approach could identify genetic tests for treatment response of other metastatic tumor types, he said.
The meeting was sponsored by the American Society of Clinical Oncology, the European Organisation for Research and Treatment of Cancer, and the National Cancer Institute. Dr. Cheung said that he is a coinventor on patents held by Memorial Sloan-Kettering Cancer Center.
On Twitter @mitchelzoler
AT THE MARKERS IN CANCER MEETING
Major finding: In a multivariate analysis, patients negative for minimal residual disease had about a fourfold increased rate of progression-free survival and about a threefold increased rate of overall survival, compared with patients positive for MRD; both differences were statistically significant.
Data source: A review of 343 patients with stage IV neuroblastoma treated with immunotherapy at one U.S. center.
Disclosures: Dr. Cheung said that he is a coinventor on patents held by Memorial Sloan-Kettering Cancer Center.
Genetic profiling transforms cancer treatment trials
BRUSSELS – The ballooning list of genetic markers linked with various cancers is spawning a radical shift in the design of oncology treatment trials.
These days, the trend is to incorporate detailed genetic analysis into the trials, so that once the results are in, researchers can try to correlate treatment responses or failures with variations in each tumor’s genetic profile.
Leaders in the field say that, ideally, the tumor of every single patient now entering a cancer treatment trial should undergo a baseline genetic analysis, either using a large panel of targeted genetic markers or full-genome sequencing – although they acknowledge that, for the time being, complete sequencing provides much more information than can be used practically.
This changing paradigm of cancer treatment trial design comes with a major, built-in limitation that seems solvable only by dramatically increasing the scope of patients enrolled in trials: Each mutational cancer "driver" seems specific for just a few percent of patients. That means making statistically meaningful correlations among the responses of patients to various drugs and their tumors’ genetic profiles requires sifting through thousands of patients, far more than usually enroll in treatment trials today.
"The big challenge is to identify the mutations or genetic alterations that help inform the results of clinical trials. There are a lot of potential genetic markers, but very few have been validated. Tumors are being sequenced, and we find lots of mutations; but we don’t yet know what to do with most of this information," said Dr. Francisco J. Esteva, professor of medicine and director of the breast medical oncology program at New York University in an interview during a meeting on markers in cancer.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
"Finding ‘actionable’ mutations is very complicated because of next-generation sequencing," Dr. Esteva added. "We have some very good inhibitor drugs" aimed at certain mutations that can be highly effective in selected patients, "but when we give these drugs to larger populations of patients, the drugs may not work."
Even though a tumor may carry a genetic mutation identified as a cancer driver and thus an effective target for drug treatment in some patients, the mutation may not be the most important driver in other patients.
"Trying to find the mutations or other genetic changes that can be effective targets for treatment sounds simple, but it’s really not so simple," noted Dr. Esteva, an organizer of the meeting, sponsored by the American Society of Clinical Oncology, the European Organization for Research and Treatment of Cancer, and the National Cancer Institute.
"We’ve been in an era where we looked at one genetic marker at a time. Now it’s pretty clear that this approach will not move us forward fast enough," said Dr. Lisa A. Carey, professor and medical director of the breast center at the University of North Carolina in Chapel Hill, and another organizer of the meeting.
"Looking at a full genetic profile of the tumor has great appeal but is also more complicated," Dr. Carey explained. "Today, we have a limited portfolio of genetic markers with known clinical significance and a limited portfolio of drugs. We’ve had some huge success stories [with targeted therapy], but it’s not simple, and it is far from solved."
"Finding a target in a patient’s tumor and having an agent that inhibits the target does not imply clinical benefit," said Dr. Shivaani Kummar, head of early clinical trials development in the division of cancer treatment and diagnosis of the National Cancer Institute.
The enormous volume of genetic information now available from next-generation sequencing, which can supply data on hundreds or even potentially thousands of individual genes for a relatively affordable price, "is affecting trial design, leading to ‘umbrella’ designs that use a variety of genetic markers and panels of several drugs," said Dr. Robert L. Becker Jr., a chief medical officer at the Center for Devices and Radiological Health of the Food and Drug Administration.
"Is the current model for development of diagnostic markers and drugs sustainable?’" Dr. Becker asked. "Next-generation sequencing is different, because it can query an almost unlimited number of analytes in a single assay."
At the meeting, a series of researchers from the United States and Europe described and discussed several recently designed drug treatment trials prospectively structured to collect wide-ranging genetic data from the tumors of enrolled patients.
One example is the MATCH (Molecular Analysis for Therapy Choice) trial, expected to start in 2014 with a goal of enrolling about 1,000 patients with solid tumors that have progressed following initial treatment with at least one drug. The investigators will use targeted mutations or amplifications as well as whole exome sequencing to try to better assign patients to their next regimen, said Dr. Kummar.
"It’s a new paradigm of trial design for cancer," said Dr. Esteva. "Going forward, all major drug trials should be designed" to include genetic analyses.
But the MATCH trial, as well as several others outlined at the meeting, will require casting large nets to find adequate numbers of appropriate patients to enroll.
"It’s a small subset of patients with each type of mutation, so getting the sample size required to get information about treatments will require a community effort," said Dr. Esteva. "It’s very important to have a lot of patients to get meaningful results." Progressing from studies with relatively small numbers of patients at academic centers to the larger populations of patients treated by community oncologists "will be one of the biggest challenges," he said.
Incorporating routine genetic analyses into trials and into routine practice also raises other issues, Dr. Carey noted. "Does the tumor evolve during treatment, so that what was found with testing at baseline is no longer the disease being treated?"
Once genetic profiling of tumors becomes routine, another challenge will be efficiently and reliably alerting physicians and patients when a genetic marker that had no known clinical consequence when it was first found in a patient’s tumor is subsequently discovered to be effectively treated with a targeted drug, she said.
And no consensus has emerged on whether it’s best to do genetic assessments of tumors using specimens collected by direct biopsy or by collecting tumor cells or tumor DNA circulating in a patient’s blood, Dr. Carey cautioned.
For now, the key step is making genetic analysis a routine part of every cancer-treatment trial. "We need tumor analyses for every patient," she said. "We should get correlates for 100% of cancers."
Dr. Becker, Dr. Carey, Dr. Esteva, and Dr. Kummar all said that they had no disclosures.
On Twitter @mitchelzoler
BRUSSELS – The ballooning list of genetic markers linked with various cancers is spawning a radical shift in the design of oncology treatment trials.
These days, the trend is to incorporate detailed genetic analysis into the trials, so that once the results are in, researchers can try to correlate treatment responses or failures with variations in each tumor’s genetic profile.
Leaders in the field say that, ideally, the tumor of every single patient now entering a cancer treatment trial should undergo a baseline genetic analysis, either using a large panel of targeted genetic markers or full-genome sequencing – although they acknowledge that, for the time being, complete sequencing provides much more information than can be used practically.
This changing paradigm of cancer treatment trial design comes with a major, built-in limitation that seems solvable only by dramatically increasing the scope of patients enrolled in trials: Each mutational cancer "driver" seems specific for just a few percent of patients. That means making statistically meaningful correlations among the responses of patients to various drugs and their tumors’ genetic profiles requires sifting through thousands of patients, far more than usually enroll in treatment trials today.
"The big challenge is to identify the mutations or genetic alterations that help inform the results of clinical trials. There are a lot of potential genetic markers, but very few have been validated. Tumors are being sequenced, and we find lots of mutations; but we don’t yet know what to do with most of this information," said Dr. Francisco J. Esteva, professor of medicine and director of the breast medical oncology program at New York University in an interview during a meeting on markers in cancer.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
"Finding ‘actionable’ mutations is very complicated because of next-generation sequencing," Dr. Esteva added. "We have some very good inhibitor drugs" aimed at certain mutations that can be highly effective in selected patients, "but when we give these drugs to larger populations of patients, the drugs may not work."
Even though a tumor may carry a genetic mutation identified as a cancer driver and thus an effective target for drug treatment in some patients, the mutation may not be the most important driver in other patients.
"Trying to find the mutations or other genetic changes that can be effective targets for treatment sounds simple, but it’s really not so simple," noted Dr. Esteva, an organizer of the meeting, sponsored by the American Society of Clinical Oncology, the European Organization for Research and Treatment of Cancer, and the National Cancer Institute.
"We’ve been in an era where we looked at one genetic marker at a time. Now it’s pretty clear that this approach will not move us forward fast enough," said Dr. Lisa A. Carey, professor and medical director of the breast center at the University of North Carolina in Chapel Hill, and another organizer of the meeting.
"Looking at a full genetic profile of the tumor has great appeal but is also more complicated," Dr. Carey explained. "Today, we have a limited portfolio of genetic markers with known clinical significance and a limited portfolio of drugs. We’ve had some huge success stories [with targeted therapy], but it’s not simple, and it is far from solved."
"Finding a target in a patient’s tumor and having an agent that inhibits the target does not imply clinical benefit," said Dr. Shivaani Kummar, head of early clinical trials development in the division of cancer treatment and diagnosis of the National Cancer Institute.
The enormous volume of genetic information now available from next-generation sequencing, which can supply data on hundreds or even potentially thousands of individual genes for a relatively affordable price, "is affecting trial design, leading to ‘umbrella’ designs that use a variety of genetic markers and panels of several drugs," said Dr. Robert L. Becker Jr., a chief medical officer at the Center for Devices and Radiological Health of the Food and Drug Administration.
"Is the current model for development of diagnostic markers and drugs sustainable?’" Dr. Becker asked. "Next-generation sequencing is different, because it can query an almost unlimited number of analytes in a single assay."
At the meeting, a series of researchers from the United States and Europe described and discussed several recently designed drug treatment trials prospectively structured to collect wide-ranging genetic data from the tumors of enrolled patients.
One example is the MATCH (Molecular Analysis for Therapy Choice) trial, expected to start in 2014 with a goal of enrolling about 1,000 patients with solid tumors that have progressed following initial treatment with at least one drug. The investigators will use targeted mutations or amplifications as well as whole exome sequencing to try to better assign patients to their next regimen, said Dr. Kummar.
"It’s a new paradigm of trial design for cancer," said Dr. Esteva. "Going forward, all major drug trials should be designed" to include genetic analyses.
But the MATCH trial, as well as several others outlined at the meeting, will require casting large nets to find adequate numbers of appropriate patients to enroll.
"It’s a small subset of patients with each type of mutation, so getting the sample size required to get information about treatments will require a community effort," said Dr. Esteva. "It’s very important to have a lot of patients to get meaningful results." Progressing from studies with relatively small numbers of patients at academic centers to the larger populations of patients treated by community oncologists "will be one of the biggest challenges," he said.
Incorporating routine genetic analyses into trials and into routine practice also raises other issues, Dr. Carey noted. "Does the tumor evolve during treatment, so that what was found with testing at baseline is no longer the disease being treated?"
Once genetic profiling of tumors becomes routine, another challenge will be efficiently and reliably alerting physicians and patients when a genetic marker that had no known clinical consequence when it was first found in a patient’s tumor is subsequently discovered to be effectively treated with a targeted drug, she said.
And no consensus has emerged on whether it’s best to do genetic assessments of tumors using specimens collected by direct biopsy or by collecting tumor cells or tumor DNA circulating in a patient’s blood, Dr. Carey cautioned.
For now, the key step is making genetic analysis a routine part of every cancer-treatment trial. "We need tumor analyses for every patient," she said. "We should get correlates for 100% of cancers."
Dr. Becker, Dr. Carey, Dr. Esteva, and Dr. Kummar all said that they had no disclosures.
On Twitter @mitchelzoler
BRUSSELS – The ballooning list of genetic markers linked with various cancers is spawning a radical shift in the design of oncology treatment trials.
These days, the trend is to incorporate detailed genetic analysis into the trials, so that once the results are in, researchers can try to correlate treatment responses or failures with variations in each tumor’s genetic profile.
Leaders in the field say that, ideally, the tumor of every single patient now entering a cancer treatment trial should undergo a baseline genetic analysis, either using a large panel of targeted genetic markers or full-genome sequencing – although they acknowledge that, for the time being, complete sequencing provides much more information than can be used practically.
This changing paradigm of cancer treatment trial design comes with a major, built-in limitation that seems solvable only by dramatically increasing the scope of patients enrolled in trials: Each mutational cancer "driver" seems specific for just a few percent of patients. That means making statistically meaningful correlations among the responses of patients to various drugs and their tumors’ genetic profiles requires sifting through thousands of patients, far more than usually enroll in treatment trials today.
"The big challenge is to identify the mutations or genetic alterations that help inform the results of clinical trials. There are a lot of potential genetic markers, but very few have been validated. Tumors are being sequenced, and we find lots of mutations; but we don’t yet know what to do with most of this information," said Dr. Francisco J. Esteva, professor of medicine and director of the breast medical oncology program at New York University in an interview during a meeting on markers in cancer.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
"Finding ‘actionable’ mutations is very complicated because of next-generation sequencing," Dr. Esteva added. "We have some very good inhibitor drugs" aimed at certain mutations that can be highly effective in selected patients, "but when we give these drugs to larger populations of patients, the drugs may not work."
Even though a tumor may carry a genetic mutation identified as a cancer driver and thus an effective target for drug treatment in some patients, the mutation may not be the most important driver in other patients.
"Trying to find the mutations or other genetic changes that can be effective targets for treatment sounds simple, but it’s really not so simple," noted Dr. Esteva, an organizer of the meeting, sponsored by the American Society of Clinical Oncology, the European Organization for Research and Treatment of Cancer, and the National Cancer Institute.
"We’ve been in an era where we looked at one genetic marker at a time. Now it’s pretty clear that this approach will not move us forward fast enough," said Dr. Lisa A. Carey, professor and medical director of the breast center at the University of North Carolina in Chapel Hill, and another organizer of the meeting.
"Looking at a full genetic profile of the tumor has great appeal but is also more complicated," Dr. Carey explained. "Today, we have a limited portfolio of genetic markers with known clinical significance and a limited portfolio of drugs. We’ve had some huge success stories [with targeted therapy], but it’s not simple, and it is far from solved."
"Finding a target in a patient’s tumor and having an agent that inhibits the target does not imply clinical benefit," said Dr. Shivaani Kummar, head of early clinical trials development in the division of cancer treatment and diagnosis of the National Cancer Institute.
The enormous volume of genetic information now available from next-generation sequencing, which can supply data on hundreds or even potentially thousands of individual genes for a relatively affordable price, "is affecting trial design, leading to ‘umbrella’ designs that use a variety of genetic markers and panels of several drugs," said Dr. Robert L. Becker Jr., a chief medical officer at the Center for Devices and Radiological Health of the Food and Drug Administration.
"Is the current model for development of diagnostic markers and drugs sustainable?’" Dr. Becker asked. "Next-generation sequencing is different, because it can query an almost unlimited number of analytes in a single assay."
At the meeting, a series of researchers from the United States and Europe described and discussed several recently designed drug treatment trials prospectively structured to collect wide-ranging genetic data from the tumors of enrolled patients.
One example is the MATCH (Molecular Analysis for Therapy Choice) trial, expected to start in 2014 with a goal of enrolling about 1,000 patients with solid tumors that have progressed following initial treatment with at least one drug. The investigators will use targeted mutations or amplifications as well as whole exome sequencing to try to better assign patients to their next regimen, said Dr. Kummar.
"It’s a new paradigm of trial design for cancer," said Dr. Esteva. "Going forward, all major drug trials should be designed" to include genetic analyses.
But the MATCH trial, as well as several others outlined at the meeting, will require casting large nets to find adequate numbers of appropriate patients to enroll.
"It’s a small subset of patients with each type of mutation, so getting the sample size required to get information about treatments will require a community effort," said Dr. Esteva. "It’s very important to have a lot of patients to get meaningful results." Progressing from studies with relatively small numbers of patients at academic centers to the larger populations of patients treated by community oncologists "will be one of the biggest challenges," he said.
Incorporating routine genetic analyses into trials and into routine practice also raises other issues, Dr. Carey noted. "Does the tumor evolve during treatment, so that what was found with testing at baseline is no longer the disease being treated?"
Once genetic profiling of tumors becomes routine, another challenge will be efficiently and reliably alerting physicians and patients when a genetic marker that had no known clinical consequence when it was first found in a patient’s tumor is subsequently discovered to be effectively treated with a targeted drug, she said.
And no consensus has emerged on whether it’s best to do genetic assessments of tumors using specimens collected by direct biopsy or by collecting tumor cells or tumor DNA circulating in a patient’s blood, Dr. Carey cautioned.
For now, the key step is making genetic analysis a routine part of every cancer-treatment trial. "We need tumor analyses for every patient," she said. "We should get correlates for 100% of cancers."
Dr. Becker, Dr. Carey, Dr. Esteva, and Dr. Kummar all said that they had no disclosures.
On Twitter @mitchelzoler
EXPERT ANALYSIS AT THE MARKERS IN CANCER MEETING
