ASCO: Cancer Research Must Change Course in 'Molecular Era'

The American Society of Clinical Oncology has issued a report calling for changes to the nation’s cancer research system that could speed delivery of more effective and personalized cancer therapies.

The society’s "blueprint" for transforming clinical and translational research focuses on three priorities: changing the way new cancer therapies are developed to emphasize molecular approaches, designing smarter and faster clinical trials, and harnessing new health information technology tools.

"One of the dominant themes emerging is this notion that all cancers are becoming rare cancers," American Society of Clinical Oncology (ASCO) president Dr. Michael Link said at a press briefing 40 years after the nation initiated the War on Cancer.

"As we learn more and more about lung cancer, we realize that at a molecular level, lung cancers that look the same under the microscope might have a profile genetically that splits that group of lung cancers into 20 different diseases. And the same is true of colon and breast cancer."

Advances in the understanding of cancer biology have already transformed the treatment of some cancers by targeting specific molecular characteristics, Dr. Link said. This is particularly true for cancers such as chronic myeloid leukemia (CML) that are driven by a single, powerful mutation. For most cancers, however, effective treatment will require targeting a combination of different genes and proteins that cause the cancer to develop and spread.

"What this means for the conduct of clinical trials is that we have to be much smarter about enriching a particular clinical trial with patients that are most likely to benefit based on what we know about the subset of lung cancer they belong to or colon cancer they belong to," he said.

The current approach to developing cancer therapies is ill equipped to capitalize on this growing understanding of cancer’s biological underpinnings, according to Dr. Link, a professor of pediatric hematology and oncology at Stanford (Calif.) University.

Specifically, drug development is hampered by researchers’ limited understanding of which molecular pathways are most important to target, and lacks many of the diagnostic tools needed to identify patients with specific mutations. At the same time, clinical trials lack the flexibility to provide quick answers about the effectiveness of therapies targeted to molecular subgroups, and have been weakened by years of underfunding and a labyrinth of regulatory requirements, he said.

One of the first steps needed to revitalize drug development is to identify and prioritize the molecular targets that have the greatest promise for improving patient survival, said Dr. Neal Meropol, one of three oncologists who served as executive editors of the report "Accelerating Progress Against Cancer: ASCO’s Blueprint for Transforming Clinical and Translational Cancer Research."

Over the next decade, the report envisions that researchers and clinicians will have the tools to quickly conduct a panomic analysis for every cancer patient that will include an examination of their genomic makeup and a complete molecular characterization of their cancer cells. The report also calls for biomarkers and diagnostic assays to be developed and validated simultaneously with cancer treatments, not as separate steps as often occurs today. Also on the agenda is the development of industry standards for biospecimens.

Getting Pharma to Collaborate. Incentives will also need to be developed to encourage industry and the research community to work together in creating new targeted therapies, including combinations of treatments that might involve different sponsors and institutions, said Dr. Meropol, chief of medical oncology at Case Western Reserve University in Cleveland.

"It’s the combination treatments that are really going to be increasingly essential, as we seek to target the multiple defects that we identify within a single patient’s tumor," he said.

When asked by reporters what would motivate pharmaceutical companies to work together to test combination treatments rather than bring their own blockbuster to market, Dr. John Mendelsohn, chair of the Institute of Medicine’s National Cancer Policy Forum, said economics will entice them. Drug companies have learned that response rates with a single targeted agent are "ho-hum," at 5% or 10%, but may be boosted when combined with another agent that targets a different facet of the molecular pathway.

"It’s not happening as much as we’d like, but it’s happening more and more," he said.

ASCO promises to collaborate with partners at the National Cancer Institute and the Institute of Medicine to convene a working group with industry, academia, and other federal agencies to "explore ways to promote a more collaborative approach to developing new prevention and therapeutic strategies," according to the report.

"One of the dominant themes emerging is this notion that all cancers are becoming rare cancers."

Pharmaceutical companies also stand to profit from a strategy that targets increasingly small subsets of cancer patients. Although there are a little more than 4,000 new cases of Philadelphia chromosome–positive CML each year, the tyrosine kinase inhibitor imatinib (Gleevec) is making a fortune for the company that developed it, Dr. Mendelsohn said.

"It’s expensive, but on the other hand it works, and the five-year survival rate has just rocketed up as a result," he said. "If it’s a good drug and it really will change outcomes, our society is willing to pay for it and it can make a profit."

Dr. Link pointed out that the efficacy of some drugs crosses tumor types, with imatinib also approved for several malignancies including Kit-positive gastrointestinal stromal tumors.

The recently approved anaplastic lymphoma kinase (ALK) inhibitor crizotinib (Xalkori) was also cited as proof that smaller trials in very select patient populations can pay off. Crizotinib pushed response rates to 61% in patients with ALK-positive non–small cell lung cancer (NSCLC), a subset that represents just 1%-7% of NSCLC patients, and may bring Pfizer annual sales of $755 million by 2015, according to analysts surveyed by Bloomberg.

Making Medical Records Do More. Part of ASCO’s vision for the next decade is that advances in health information technology would deliver up-to-the-minute personalized information and save patients from repeating their medical history every time they see a new doctor, Dr. Link said. The data would be linked to national treatment guidelines that would prompt physicians on what national experts view as the appropriate course of treatment.

At the same time, linkage to clinical trial databases would trigger notification of suitable clinical trials based on available data about the patient’s clinical condition and course. On the back end, patient data would be fed into registries that could be analyzed by researchers for clues, not just for clinical trials but for routine care, he said.

The authors did not disclose any conflicts of interest.

The American Society of Clinical Oncology has issued a report calling for changes to the nation’s cancer research system that could speed delivery of more effective and personalized cancer therapies.

The society’s "blueprint" for transforming clinical and translational research focuses on three priorities: changing the way new cancer therapies are developed to emphasize molecular approaches, designing smarter and faster clinical trials, and harnessing new health information technology tools.

"One of the dominant themes emerging is this notion that all cancers are becoming rare cancers," American Society of Clinical Oncology (ASCO) president Dr. Michael Link said at a press briefing 40 years after the nation initiated the War on Cancer.

"As we learn more and more about lung cancer, we realize that at a molecular level, lung cancers that look the same under the microscope might have a profile genetically that splits that group of lung cancers into 20 different diseases. And the same is true of colon and breast cancer."

Advances in the understanding of cancer biology have already transformed the treatment of some cancers by targeting specific molecular characteristics, Dr. Link said. This is particularly true for cancers such as chronic myeloid leukemia (CML) that are driven by a single, powerful mutation. For most cancers, however, effective treatment will require targeting a combination of different genes and proteins that cause the cancer to develop and spread.

"What this means for the conduct of clinical trials is that we have to be much smarter about enriching a particular clinical trial with patients that are most likely to benefit based on what we know about the subset of lung cancer they belong to or colon cancer they belong to," he said.

The current approach to developing cancer therapies is ill equipped to capitalize on this growing understanding of cancer’s biological underpinnings, according to Dr. Link, a professor of pediatric hematology and oncology at Stanford (Calif.) University.

Specifically, drug development is hampered by researchers’ limited understanding of which molecular pathways are most important to target, and lacks many of the diagnostic tools needed to identify patients with specific mutations. At the same time, clinical trials lack the flexibility to provide quick answers about the effectiveness of therapies targeted to molecular subgroups, and have been weakened by years of underfunding and a labyrinth of regulatory requirements, he said.

One of the first steps needed to revitalize drug development is to identify and prioritize the molecular targets that have the greatest promise for improving patient survival, said Dr. Neal Meropol, one of three oncologists who served as executive editors of the report "Accelerating Progress Against Cancer: ASCO’s Blueprint for Transforming Clinical and Translational Cancer Research."

Over the next decade, the report envisions that researchers and clinicians will have the tools to quickly conduct a panomic analysis for every cancer patient that will include an examination of their genomic makeup and a complete molecular characterization of their cancer cells. The report also calls for biomarkers and diagnostic assays to be developed and validated simultaneously with cancer treatments, not as separate steps as often occurs today. Also on the agenda is the development of industry standards for biospecimens.

Getting Pharma to Collaborate. Incentives will also need to be developed to encourage industry and the research community to work together in creating new targeted therapies, including combinations of treatments that might involve different sponsors and institutions, said Dr. Meropol, chief of medical oncology at Case Western Reserve University in Cleveland.

"It’s the combination treatments that are really going to be increasingly essential, as we seek to target the multiple defects that we identify within a single patient’s tumor," he said.

When asked by reporters what would motivate pharmaceutical companies to work together to test combination treatments rather than bring their own blockbuster to market, Dr. John Mendelsohn, chair of the Institute of Medicine’s National Cancer Policy Forum, said economics will entice them. Drug companies have learned that response rates with a single targeted agent are "ho-hum," at 5% or 10%, but may be boosted when combined with another agent that targets a different facet of the molecular pathway.

"It’s not happening as much as we’d like, but it’s happening more and more," he said.

ASCO promises to collaborate with partners at the National Cancer Institute and the Institute of Medicine to convene a working group with industry, academia, and other federal agencies to "explore ways to promote a more collaborative approach to developing new prevention and therapeutic strategies," according to the report.

"One of the dominant themes emerging is this notion that all cancers are becoming rare cancers."

Pharmaceutical companies also stand to profit from a strategy that targets increasingly small subsets of cancer patients. Although there are a little more than 4,000 new cases of Philadelphia chromosome–positive CML each year, the tyrosine kinase inhibitor imatinib (Gleevec) is making a fortune for the company that developed it, Dr. Mendelsohn said.

"It’s expensive, but on the other hand it works, and the five-year survival rate has just rocketed up as a result," he said. "If it’s a good drug and it really will change outcomes, our society is willing to pay for it and it can make a profit."

Dr. Link pointed out that the efficacy of some drugs crosses tumor types, with imatinib also approved for several malignancies including Kit-positive gastrointestinal stromal tumors.

The recently approved anaplastic lymphoma kinase (ALK) inhibitor crizotinib (Xalkori) was also cited as proof that smaller trials in very select patient populations can pay off. Crizotinib pushed response rates to 61% in patients with ALK-positive non–small cell lung cancer (NSCLC), a subset that represents just 1%-7% of NSCLC patients, and may bring Pfizer annual sales of $755 million by 2015, according to analysts surveyed by Bloomberg.

Making Medical Records Do More. Part of ASCO’s vision for the next decade is that advances in health information technology would deliver up-to-the-minute personalized information and save patients from repeating their medical history every time they see a new doctor, Dr. Link said. The data would be linked to national treatment guidelines that would prompt physicians on what national experts view as the appropriate course of treatment.

At the same time, linkage to clinical trial databases would trigger notification of suitable clinical trials based on available data about the patient’s clinical condition and course. On the back end, patient data would be fed into registries that could be analyzed by researchers for clues, not just for clinical trials but for routine care, he said.

The authors did not disclose any conflicts of interest.

The American Society of Clinical Oncology has issued a report calling for changes to the nation’s cancer research system that could speed delivery of more effective and personalized cancer therapies.

The society’s "blueprint" for transforming clinical and translational research focuses on three priorities: changing the way new cancer therapies are developed to emphasize molecular approaches, designing smarter and faster clinical trials, and harnessing new health information technology tools.

"One of the dominant themes emerging is this notion that all cancers are becoming rare cancers," American Society of Clinical Oncology (ASCO) president Dr. Michael Link said at a press briefing 40 years after the nation initiated the War on Cancer.

"As we learn more and more about lung cancer, we realize that at a molecular level, lung cancers that look the same under the microscope might have a profile genetically that splits that group of lung cancers into 20 different diseases. And the same is true of colon and breast cancer."

Advances in the understanding of cancer biology have already transformed the treatment of some cancers by targeting specific molecular characteristics, Dr. Link said. This is particularly true for cancers such as chronic myeloid leukemia (CML) that are driven by a single, powerful mutation. For most cancers, however, effective treatment will require targeting a combination of different genes and proteins that cause the cancer to develop and spread.

"What this means for the conduct of clinical trials is that we have to be much smarter about enriching a particular clinical trial with patients that are most likely to benefit based on what we know about the subset of lung cancer they belong to or colon cancer they belong to," he said.

The current approach to developing cancer therapies is ill equipped to capitalize on this growing understanding of cancer’s biological underpinnings, according to Dr. Link, a professor of pediatric hematology and oncology at Stanford (Calif.) University.

Specifically, drug development is hampered by researchers’ limited understanding of which molecular pathways are most important to target, and lacks many of the diagnostic tools needed to identify patients with specific mutations. At the same time, clinical trials lack the flexibility to provide quick answers about the effectiveness of therapies targeted to molecular subgroups, and have been weakened by years of underfunding and a labyrinth of regulatory requirements, he said.

One of the first steps needed to revitalize drug development is to identify and prioritize the molecular targets that have the greatest promise for improving patient survival, said Dr. Neal Meropol, one of three oncologists who served as executive editors of the report "Accelerating Progress Against Cancer: ASCO’s Blueprint for Transforming Clinical and Translational Cancer Research."

Over the next decade, the report envisions that researchers and clinicians will have the tools to quickly conduct a panomic analysis for every cancer patient that will include an examination of their genomic makeup and a complete molecular characterization of their cancer cells. The report also calls for biomarkers and diagnostic assays to be developed and validated simultaneously with cancer treatments, not as separate steps as often occurs today. Also on the agenda is the development of industry standards for biospecimens.

Getting Pharma to Collaborate. Incentives will also need to be developed to encourage industry and the research community to work together in creating new targeted therapies, including combinations of treatments that might involve different sponsors and institutions, said Dr. Meropol, chief of medical oncology at Case Western Reserve University in Cleveland.

"It’s the combination treatments that are really going to be increasingly essential, as we seek to target the multiple defects that we identify within a single patient’s tumor," he said.

When asked by reporters what would motivate pharmaceutical companies to work together to test combination treatments rather than bring their own blockbuster to market, Dr. John Mendelsohn, chair of the Institute of Medicine’s National Cancer Policy Forum, said economics will entice them. Drug companies have learned that response rates with a single targeted agent are "ho-hum," at 5% or 10%, but may be boosted when combined with another agent that targets a different facet of the molecular pathway.

"It’s not happening as much as we’d like, but it’s happening more and more," he said.

ASCO promises to collaborate with partners at the National Cancer Institute and the Institute of Medicine to convene a working group with industry, academia, and other federal agencies to "explore ways to promote a more collaborative approach to developing new prevention and therapeutic strategies," according to the report.

"One of the dominant themes emerging is this notion that all cancers are becoming rare cancers."

Pharmaceutical companies also stand to profit from a strategy that targets increasingly small subsets of cancer patients. Although there are a little more than 4,000 new cases of Philadelphia chromosome–positive CML each year, the tyrosine kinase inhibitor imatinib (Gleevec) is making a fortune for the company that developed it, Dr. Mendelsohn said.

"It’s expensive, but on the other hand it works, and the five-year survival rate has just rocketed up as a result," he said. "If it’s a good drug and it really will change outcomes, our society is willing to pay for it and it can make a profit."

Dr. Link pointed out that the efficacy of some drugs crosses tumor types, with imatinib also approved for several malignancies including Kit-positive gastrointestinal stromal tumors.

The recently approved anaplastic lymphoma kinase (ALK) inhibitor crizotinib (Xalkori) was also cited as proof that smaller trials in very select patient populations can pay off. Crizotinib pushed response rates to 61% in patients with ALK-positive non–small cell lung cancer (NSCLC), a subset that represents just 1%-7% of NSCLC patients, and may bring Pfizer annual sales of $755 million by 2015, according to analysts surveyed by Bloomberg.

Making Medical Records Do More. Part of ASCO’s vision for the next decade is that advances in health information technology would deliver up-to-the-minute personalized information and save patients from repeating their medical history every time they see a new doctor, Dr. Link said. The data would be linked to national treatment guidelines that would prompt physicians on what national experts view as the appropriate course of treatment.

At the same time, linkage to clinical trial databases would trigger notification of suitable clinical trials based on available data about the patient’s clinical condition and course. On the back end, patient data would be fed into registries that could be analyzed by researchers for clues, not just for clinical trials but for routine care, he said.

The authors did not disclose any conflicts of interest.