ASCO panel: Precision medicine in practice can be challenging

Suzanne Topalian
Richard Schilsky
Richard L. Schilsky

Choosing the appropriate genetic tests and managing patient expectations can be challenges clinicians face when implementing precision medicine, according to a panel discussion hosted by ASCO.

Twenty years ago, trastuzumab (Herceptin, Genentech) was the first monoclonal human antibody approved for HER-2-positive breast cancer, marking the beginning of what has come to be known as precision medicine.

Precision medicine encompasses at least three areas, including:

  • next-generation sequencing of tumor DNA leading to targeted therapies;
  • creating subsets of various diseases, allowing for greater prediction of outcomes; and
  • immunotherapies, including vaccines and engineered cellular therapies.

Precision medicine has been marked by FDA approvals of gene mutation-specific treatments, such as afatinib (Gilotrif, Boehringer Ingelheim) — an oral, once-daily EGFR tyrosine kinase inhibitor — which is indicated for the first-line treatment of patients with non-small cell lung cancer whose tumors have certain EGFR mutations.

“For a long time, people thought that [immunotherapy and targeted therapies] were two entirely different fields, and people were working in isolation at the beginning,” Suzanne Topalian, MD, melanoma program director at Johns Hopkins University, said during the panel. “I’m an immunologist; I didn’t know that there were many people working on molecular biology and targeted drugs. There are a lot of intersections between these two areas, and I think the hallmark of this intersection came last May when the FDA had a landmark approval to give immunotherapy to patients who had a genetic marker in their tumor. That is the intersection — the meeting of cancer genetics and cancer immunology.”

For effective implementation, precision medicine in practice requires the intersections of several fields and key elements, such as genomic testing facilities, according to panel moderator Richard L. Schilsky, MD, FASCO, FACP, chief medical officer of ASCO.

 

Determining the right test

Because there are many genetic tests available, clinicians may have a difficult time determining the right test.

“There are a lot of genetic tests out there, and they range from testing for a specific alteration and a specific gene to these large panel tests that report out findings on many hundreds of genes all at the same time,” Schilsky said.

Guidelines from the National Comprehensive Cancer Network and other professional groups can help direct physicians to the best genetic tests, according to Anna B. Berry, MD, pathologist and scientific director of the personalized medicine program at Swedish Cancer Institute in Seattle.

Genomic tests must be Clinical Laboratory Improvement Amendments-approved, and many are College of American Pathologists certified, although this is not a requirement.

Just like with drug products, clinicians should be cautious about genetic tests being offered and should evaluate them carefully, according to Berry.

When a company offers a genomic test, “clinicians should say, show me your validation data; show me how you’re meeting all the parameters that you should be meeting,” Berry said. “Aside from that, clinicians need to look at the report. What kind of information are you giving back to me?”

Some genomic testing reports include information on hundreds of genes, which can be overwhelming for clinicians.

 

 

Otis Brawley
Otis Brawley

“Depending on how you count it up, there’s only about 30 or 40 genes right now that are clinically actionable with currently available therapies, and yet we’re getting reports with 300 or 400 to 600 genes,” Schilsky said. “Doctors are really struggling with what to do with all this information.”

A multidisciplinary approach can help clinicians wade through this information. Pathologists, in particular, can help relay to doctors which genes are important and which can be ignored for now, Berry said.

“We all need to work together,” she added. “Pathologists need to be better informed, clinicians need to be better informed and we need to talk to each other. Good communication is the best part.”

Genomic testing can also be used to determine a patients’ risk for certain cancers.

Otis Brawley, MD, MACP, FASCO, FACE, chief medical officer at the American Cancer Society, and HemOnc Today Editorial Board Member, expressed caution about using these tests too often. Specifically, relying on genomic testing could lead to overdiagnosis and overtreatment among those at low risk for cancer. He recommended screening those who are at high risk and using the genetic test to encourage healthier behaviors.

“We can use genetics and genomics to actually steer people toward healthier behaviors such that they might be less likely to get the disease,” Brawley said. “If you can focus on people who are at high risk for a cancer and say these people need to be screened, and these people who are at lower risk don’t need to be screened, we can get a little bit more efficient.”

 

Acting on genetic data

To deliver precision medicine, a practice needs genomic testing facilities, experts who can help interpret the test results and access to the therapies.

Barbara McAneny
Barbara L. McAneny

Several panelists discussed their tactics for managing their precision medicine practices.

“In the community, we need the decision support to be able to not only remember which mutation to think about in a given tumor type, and you can’t memorize this,” Barbara L. McAneny, MD, CEO of New Mexico Oncology Hematology Consultants and president-elect of AMA, said. “What we have done — in my practice and working with a series of other practices across the country — is create pathways.”

These pathways act as a decision support tool for physicians to know the right genomic test to use for each patient based on the progression of their disease, and they recommend treatments based on the test results.

These pathways can also receive prior authorization by payers, which expedites the process of getting the test and treatment to the patient.

 

 

“A month is a long time for a cancer patient to wait. It’s not acceptable,” McAneny said. “So, we have to streamline that process, and I think pathways are the way to do that.”

Lincoln D. Nadauld, MD, PhD, medical director of cancer genomics at Intermountain Healthcare, and colleagues established an entirely in-house precision medicine unit, including their own genetic testing capabilities, to bring the best care to their patients in the community.

“These genomic tests to most physicians read like Greek,” Nadauld said. “They’re difficult to discern and physicians, frankly, do not have time to look past the common ones they understand like HER-2 and EGFR.

To address this problem, Nadauld and colleagues also developed a molecular tumor board, which helps frontline physicians interpret the genomic tests and make treatment recommendations.

Edward S. Kim
Edward S. Kim

Edward S. Kim, MD, chair of solid tumor oncology and investigational therapeutics at Levine Cancer Institute of Carolinas HealthCare System and a HemOnc Today Editorial Board Member, and colleagues also use an in-house molecular tumor board that reviews the raw data of every molecular test.

For clinicians without access to their own molecular tumor board, pathways like those McAneny uses, as well as large-scale data sharing, may be helpful.

“I believe the answer to this is data sharing. If we can share data among institutions so that I, in Salt Lake City, can see which mutations and which drugs patients get and how long they’re on those and how well they do in Boston or Miami or Seattle or San Francisco, that would make me a lot smarter in my frontline patient care,” Nadauld said. “I think that’s how we start to overcome this need for molecular tumor boards is by just sharing data openly, so that we can see firsthand how patients do.”

Predictive and treatment algorithms are another available decision-support tool. These algorithms allow clinicians to input genomic data, clinical data and tumor information and then receive a treatment recommendation. However, these algorithms are not regulated by the FDA.

Robert Califf

Former FDA Commissioner Robert Califf, MD, vice chancellor for health data science at Duke Health and consultant for Verily, said the FDA will monitor algorithms related to significant diseases, but they won’t be regulated so as to not slow down the process of helping clinicians.

“These things are going to work better and better,” Califf said. “There is going to be a playing field of competition to determine the best algorithms. But, ultimately, as they get used more, there will be some catastrophes that occur because people will depend on them. We’ll learn through the problems how they really need to be regulated.”

 

 

Patient experience

Precision medicine also can be difficult for patients to navigate, particularly in terms of costs of the new immunotherapies and genomic tests.

With a personalized form of medicine comes the difficulty of expressing the importance of each patients’ therapies to insurance companies and other payers.

“We now have a personalized medicine but a completely impersonal payment system,” Robert W. Dubois, MD, PhD, chief science officer and executive vice president of the National Pharmaceutical Council, said during the panel. “We want to put fewer barriers in front of the patient who has an opportunity for curative or really effective, high-value therapies but, unfortunately, we have a really impersonalized payment system.”

Nadauld and colleagues found that precision medicine improved PFS and lowered the cost per week ($4,665 vs. $5,000), according to a sub-analysis of patients who received care at Intermountain Healthcare System (n = 44).

When asked about the value of precision medicine, DuBois said, “Clearly, as you’re targeting things tighter and tighter and you’re getting longer outcomes with fewer adverse events, there is no question that the value proposition goes up ... way more than the cost equation. ... Personalized medicine is absolutely driving us to a crisper value proposition.”

Most panelists agreed that the payment system lags behind innovations of precision medicine and that making the process easier — whether through prior-authorized pathways or value-based reimbursement — needs to be addressed.

During the panel, Meg Gaines, JD, attorney, cancer survivor and founder of the Center for Patient Partnerships at University of Wisconsin, shared several concerns about precision medicine from the patient’s perspective including:

  • access to these therapies for patients treated at nonacademic centers;
  • how genomic data is stored/used and the risks of giving samples to a testing laboratory; and
  • disclosure of genomic information to patients that may not be useful or solicited.

Gaines also expressed concerns that precision medicine is not personalized medicine, which may cause confusion for patients.

“Precision medicine is, in fact, not about ‘me’ but about subgrouping,” she said. “That confusion leads to feelings of stupidity, where patients can’t or don’t understand all of this important fancy cancer stuff. This enhances the fear and dependence on physicians that patients are trying to come up out of.”

Supportive oncology can help curb patients’ expectations and fears about precision medicine, Kim said.

Nadauld said his precision medicine department uses the molecular tumor board, treatment recommendations and navigation nurses, who explain the genomic testing.

In order to prevent high patient expectations, McAneny makes sure all of her patients know the pros and cons well enough that they could explain them to others.

“We’ve dealt with bad expectations and sad outcomes in oncology from the beginning of my career until now, and I find that [precision medicine and immunotherapies are] not different in that patients need to know everything is not fool-proof from the beginning,” she said.

 

Sharing data

For clinicians to learn the necessary information to execute precision medicine and to make treatments more affordable and streamlined, institutions must share data, according to several panelists.

There are already several consortia of data from across institutions, including ASCO’s TAPUR and the NCI’s MATCH trials.

However, institutions must continue to share data to build better pathways, show payers that precision medicine works and improve patient care.

“We need to share not only genomic data, but clinical data. That’s really key if we’re going to find out about the outcomes and the value,” Berry said. “Industry, public hospitals, private hospitals, academic hospitals — we need to get more on the same page or at least in the same room.”

Overall, the panelists expressed excitement about the potential of precision medicine.

“Not only does precision medicine hold extraordinary progress and not only has it already transformed how some cancers are treated, diagnosed and studied, but its promise has only been minimally exploited so far,” Clifford A. Hudis, MD, FASCO, FACP, CEO of ASCO, said.

“The benefits of precision medicine ... even the ones we’ve gained, don’t yet reach everyone who could benefit,” he added. “As it advances, some of these disparities that we’re already seeing in access and benefits may worsen. So, we want to explore this area of challenge together.” – by Cassie Homer

Reference:

Haslem DS, et al. J Oncol Pract. 2017;doi:10.1200/JOP.2016.011486.

Disclosures: HemOnc Today could not confirm the panelists’ disclosures at the time of publication.

Suzanne Topalian
Richard Schilsky
Richard L. Schilsky

Choosing the appropriate genetic tests and managing patient expectations can be challenges clinicians face when implementing precision medicine, according to a panel discussion hosted by ASCO.

Twenty years ago, trastuzumab (Herceptin, Genentech) was the first monoclonal human antibody approved for HER-2-positive breast cancer, marking the beginning of what has come to be known as precision medicine.

Precision medicine encompasses at least three areas, including:

  • next-generation sequencing of tumor DNA leading to targeted therapies;
  • creating subsets of various diseases, allowing for greater prediction of outcomes; and
  • immunotherapies, including vaccines and engineered cellular therapies.

Precision medicine has been marked by FDA approvals of gene mutation-specific treatments, such as afatinib (Gilotrif, Boehringer Ingelheim) — an oral, once-daily EGFR tyrosine kinase inhibitor — which is indicated for the first-line treatment of patients with non-small cell lung cancer whose tumors have certain EGFR mutations.

“For a long time, people thought that [immunotherapy and targeted therapies] were two entirely different fields, and people were working in isolation at the beginning,” Suzanne Topalian, MD, melanoma program director at Johns Hopkins University, said during the panel. “I’m an immunologist; I didn’t know that there were many people working on molecular biology and targeted drugs. There are a lot of intersections between these two areas, and I think the hallmark of this intersection came last May when the FDA had a landmark approval to give immunotherapy to patients who had a genetic marker in their tumor. That is the intersection — the meeting of cancer genetics and cancer immunology.”

For effective implementation, precision medicine in practice requires the intersections of several fields and key elements, such as genomic testing facilities, according to panel moderator Richard L. Schilsky, MD, FASCO, FACP, chief medical officer of ASCO.

 

Determining the right test

Because there are many genetic tests available, clinicians may have a difficult time determining the right test.

“There are a lot of genetic tests out there, and they range from testing for a specific alteration and a specific gene to these large panel tests that report out findings on many hundreds of genes all at the same time,” Schilsky said.

Guidelines from the National Comprehensive Cancer Network and other professional groups can help direct physicians to the best genetic tests, according to Anna B. Berry, MD, pathologist and scientific director of the personalized medicine program at Swedish Cancer Institute in Seattle.

Genomic tests must be Clinical Laboratory Improvement Amendments-approved, and many are College of American Pathologists certified, although this is not a requirement.

Just like with drug products, clinicians should be cautious about genetic tests being offered and should evaluate them carefully, according to Berry.

When a company offers a genomic test, “clinicians should say, show me your validation data; show me how you’re meeting all the parameters that you should be meeting,” Berry said. “Aside from that, clinicians need to look at the report. What kind of information are you giving back to me?”

Some genomic testing reports include information on hundreds of genes, which can be overwhelming for clinicians.

 

PAGE BREAK

 

Otis Brawley
Otis Brawley

“Depending on how you count it up, there’s only about 30 or 40 genes right now that are clinically actionable with currently available therapies, and yet we’re getting reports with 300 or 400 to 600 genes,” Schilsky said. “Doctors are really struggling with what to do with all this information.”

A multidisciplinary approach can help clinicians wade through this information. Pathologists, in particular, can help relay to doctors which genes are important and which can be ignored for now, Berry said.

“We all need to work together,” she added. “Pathologists need to be better informed, clinicians need to be better informed and we need to talk to each other. Good communication is the best part.”

Genomic testing can also be used to determine a patients’ risk for certain cancers.

Otis Brawley, MD, MACP, FASCO, FACE, chief medical officer at the American Cancer Society, and HemOnc Today Editorial Board Member, expressed caution about using these tests too often. Specifically, relying on genomic testing could lead to overdiagnosis and overtreatment among those at low risk for cancer. He recommended screening those who are at high risk and using the genetic test to encourage healthier behaviors.

“We can use genetics and genomics to actually steer people toward healthier behaviors such that they might be less likely to get the disease,” Brawley said. “If you can focus on people who are at high risk for a cancer and say these people need to be screened, and these people who are at lower risk don’t need to be screened, we can get a little bit more efficient.”

 

Acting on genetic data

To deliver precision medicine, a practice needs genomic testing facilities, experts who can help interpret the test results and access to the therapies.

Barbara McAneny
Barbara L. McAneny

Several panelists discussed their tactics for managing their precision medicine practices.

“In the community, we need the decision support to be able to not only remember which mutation to think about in a given tumor type, and you can’t memorize this,” Barbara L. McAneny, MD, CEO of New Mexico Oncology Hematology Consultants and president-elect of AMA, said. “What we have done — in my practice and working with a series of other practices across the country — is create pathways.”

These pathways act as a decision support tool for physicians to know the right genomic test to use for each patient based on the progression of their disease, and they recommend treatments based on the test results.

These pathways can also receive prior authorization by payers, which expedites the process of getting the test and treatment to the patient.

 

PAGE BREAK

 

“A month is a long time for a cancer patient to wait. It’s not acceptable,” McAneny said. “So, we have to streamline that process, and I think pathways are the way to do that.”

Lincoln D. Nadauld, MD, PhD, medical director of cancer genomics at Intermountain Healthcare, and colleagues established an entirely in-house precision medicine unit, including their own genetic testing capabilities, to bring the best care to their patients in the community.

“These genomic tests to most physicians read like Greek,” Nadauld said. “They’re difficult to discern and physicians, frankly, do not have time to look past the common ones they understand like HER-2 and EGFR.

To address this problem, Nadauld and colleagues also developed a molecular tumor board, which helps frontline physicians interpret the genomic tests and make treatment recommendations.

Edward S. Kim
Edward S. Kim

Edward S. Kim, MD, chair of solid tumor oncology and investigational therapeutics at Levine Cancer Institute of Carolinas HealthCare System and a HemOnc Today Editorial Board Member, and colleagues also use an in-house molecular tumor board that reviews the raw data of every molecular test.

For clinicians without access to their own molecular tumor board, pathways like those McAneny uses, as well as large-scale data sharing, may be helpful.

“I believe the answer to this is data sharing. If we can share data among institutions so that I, in Salt Lake City, can see which mutations and which drugs patients get and how long they’re on those and how well they do in Boston or Miami or Seattle or San Francisco, that would make me a lot smarter in my frontline patient care,” Nadauld said. “I think that’s how we start to overcome this need for molecular tumor boards is by just sharing data openly, so that we can see firsthand how patients do.”

Predictive and treatment algorithms are another available decision-support tool. These algorithms allow clinicians to input genomic data, clinical data and tumor information and then receive a treatment recommendation. However, these algorithms are not regulated by the FDA.

Robert Califf

Former FDA Commissioner Robert Califf, MD, vice chancellor for health data science at Duke Health and consultant for Verily, said the FDA will monitor algorithms related to significant diseases, but they won’t be regulated so as to not slow down the process of helping clinicians.

“These things are going to work better and better,” Califf said. “There is going to be a playing field of competition to determine the best algorithms. But, ultimately, as they get used more, there will be some catastrophes that occur because people will depend on them. We’ll learn through the problems how they really need to be regulated.”

 

PAGE BREAK

 

Patient experience

Precision medicine also can be difficult for patients to navigate, particularly in terms of costs of the new immunotherapies and genomic tests.

With a personalized form of medicine comes the difficulty of expressing the importance of each patients’ therapies to insurance companies and other payers.

“We now have a personalized medicine but a completely impersonal payment system,” Robert W. Dubois, MD, PhD, chief science officer and executive vice president of the National Pharmaceutical Council, said during the panel. “We want to put fewer barriers in front of the patient who has an opportunity for curative or really effective, high-value therapies but, unfortunately, we have a really impersonalized payment system.”

Nadauld and colleagues found that precision medicine improved PFS and lowered the cost per week ($4,665 vs. $5,000), according to a sub-analysis of patients who received care at Intermountain Healthcare System (n = 44).

When asked about the value of precision medicine, DuBois said, “Clearly, as you’re targeting things tighter and tighter and you’re getting longer outcomes with fewer adverse events, there is no question that the value proposition goes up ... way more than the cost equation. ... Personalized medicine is absolutely driving us to a crisper value proposition.”

Most panelists agreed that the payment system lags behind innovations of precision medicine and that making the process easier — whether through prior-authorized pathways or value-based reimbursement — needs to be addressed.

During the panel, Meg Gaines, JD, attorney, cancer survivor and founder of the Center for Patient Partnerships at University of Wisconsin, shared several concerns about precision medicine from the patient’s perspective including:

  • access to these therapies for patients treated at nonacademic centers;
  • how genomic data is stored/used and the risks of giving samples to a testing laboratory; and
  • disclosure of genomic information to patients that may not be useful or solicited.

Gaines also expressed concerns that precision medicine is not personalized medicine, which may cause confusion for patients.

“Precision medicine is, in fact, not about ‘me’ but about subgrouping,” she said. “That confusion leads to feelings of stupidity, where patients can’t or don’t understand all of this important fancy cancer stuff. This enhances the fear and dependence on physicians that patients are trying to come up out of.”

Supportive oncology can help curb patients’ expectations and fears about precision medicine, Kim said.

PAGE BREAK

Nadauld said his precision medicine department uses the molecular tumor board, treatment recommendations and navigation nurses, who explain the genomic testing.

In order to prevent high patient expectations, McAneny makes sure all of her patients know the pros and cons well enough that they could explain them to others.

“We’ve dealt with bad expectations and sad outcomes in oncology from the beginning of my career until now, and I find that [precision medicine and immunotherapies are] not different in that patients need to know everything is not fool-proof from the beginning,” she said.

 

Sharing data

For clinicians to learn the necessary information to execute precision medicine and to make treatments more affordable and streamlined, institutions must share data, according to several panelists.

There are already several consortia of data from across institutions, including ASCO’s TAPUR and the NCI’s MATCH trials.

However, institutions must continue to share data to build better pathways, show payers that precision medicine works and improve patient care.

“We need to share not only genomic data, but clinical data. That’s really key if we’re going to find out about the outcomes and the value,” Berry said. “Industry, public hospitals, private hospitals, academic hospitals — we need to get more on the same page or at least in the same room.”

Overall, the panelists expressed excitement about the potential of precision medicine.

“Not only does precision medicine hold extraordinary progress and not only has it already transformed how some cancers are treated, diagnosed and studied, but its promise has only been minimally exploited so far,” Clifford A. Hudis, MD, FASCO, FACP, CEO of ASCO, said.

“The benefits of precision medicine ... even the ones we’ve gained, don’t yet reach everyone who could benefit,” he added. “As it advances, some of these disparities that we’re already seeing in access and benefits may worsen. So, we want to explore this area of challenge together.” – by Cassie Homer

Reference:

Haslem DS, et al. J Oncol Pract. 2017;doi:10.1200/JOP.2016.011486.

Disclosures: HemOnc Today could not confirm the panelists’ disclosures at the time of publication.