EditorialPublication Exclusive

Precision cancer care: The knowledge (and reality) gap

Almost every day my email and regular mail have at least one article related to the growth of precision cancer care; the promise of genomics and proteomics in identifying individualized, molecularly targeted therapies; and the use of real-time “big data” to inform treatment decisions for patients.

A few years back, these articles mostly appeared in peer-reviewed journals. That, of course, has changed. Although the peer-reviewed literature in this area continues to expand rapidly, I now receive information from other authoritative publications (such as HemOnc Today), as well as marketing materials from health care organizations and major cancer centers. I am also starting to see some commercial organizations increase their marketing of genomic products.

The excitement around the use of genomic and other tumor-derived data to allow for personalized cancer care is remarkable and completely justified — few of us doubt that these approaches will transform the care of cancer and many other diseases in the next few years.

Routine genomic testing

Along with this growing excitement, I sometimes feel some anxiety — and even insecurity — especially when I look at my colleagues in solid tumor oncology. For them, genomic testing and selection of molecularly targeted therapies based on these results is becoming relatively routine. In the lymphoma world, we have been somewhat behind the curve in this respect, although molecular subtyping of some lymphoma types will probably gain increasing clinical utility in the next few years. So, although I have a rudimentary understanding of the techniques, limitations and clinical utility of some of the somatic molecular analyses now available for our patients, my understanding of how my solid tumor colleagues apply these data in their clinical practice outside the trial setting and how these data influence outcomes is limited.

John Sweetenham, MD
John Sweetenham

I will be the first to acknowledge that my colleagues in solid tumor oncology — and, for that matter, in hematologic malignancy — are smarter than me, but I can gain some consolation in knowing that I am not alone. At least one study of oncologists’ attitudes and understanding of somatic genomic tests, conducted at a major NCI-designated cancer center, demonstrated a wide range of genomic knowledge, differing attitudes toward the disclosure of genomic information — especially if the significance is unknown — to patients, and uncertainty surrounding the clinical utility of these tests. Similar data have been reported from other studies of cancer specialists in academic and community settings, suggesting that a major knowledge gap may still exist.

It’s safe to assume that if there is a need for more education for those of us taking care of cancer patients, there is probably an opportunity to improve the information we provide to our patients and families, as well. This was brought home to me when I picked up on a recent article in The Wall Street Journal that labeled laboratory testing as the “‘Wild West’ of medicine.” The overall theme of the article was directed at a call for tighter regulation of lab-developed tests.

The article cited an excellent study recently published in Journal of the National Cancer Institute that explored the Internet marketing of personalized cancer care — specifically genomic testing — by for-profit companies, research institutes, academic cancer centers, hospitals and physician groups. These groups provide a range of services, including germline and somatic testing and, in some cases, interpretive services and personalized cancer care.

Several of the websites examined market-established tests that are backed by national guidelines, including testing for BRAF and EGFR, but overall, the websites were more likely to market nonstandard tests — more than 80% of all the sites that specified tumor testing identified nonstandard tests. Commercial websites were more likely than others to market chemotherapy-sensitivity testing and, of all the websites examined, 85% provided information about the benefits of genetic testing, whereas only 27% provided information on limitations of the techniques.

The authors of this study also reported that few of the marketed somatic tests have been shown to have true clinical utility, and some of the sites offered tests that organizations such as ASCO have already concluded have insufficient evidence to support their use.

All of this is particularly sobering in the context of data that show direct-to-consumer marketing drives more patients to undergo genetic testing, even though many of them may not have the resources to interpret and understand the significance of the results. The evidence cited above suggests that they may not be able to rely on us, their oncologists, to give them reliable, fully informed guidance.

Reality gap

Tighter regulation could certainly go a long way toward limiting unnecessary and uninformative testing, but the spectrum of tests with proven clinical utility is likely to increase rapidly. Enhanced education of providers to raise their so-called “genomic confidence,” coupled with improved clinical decision support tools (of which many are now in various stages of development), will help to overcome the knowledge gap.

Overcoming the reality gap may be more challenging. As we embrace value-based cancer care, the true clinical impact of genomically driven treatment decisions will become a major determinant of the uptake of these tests. Some of the available genomic tests already have price points in excess of $10,000, and many of the molecularly targeted therapies cost more than (in some cases, much more than) $10,000 per month. Yet, for most, the clinical benefit appears to be limited to sometimes modest improvements in PFS, with no OS benefit and no suggestion that these treatments will be curative.

Hopefully, genomic testing will allow the use of these costly therapies to be limited to those patients most likely to derive benefit. If so, this should be a positive step toward delivering high-value cancer care. The recently updated FDA label for the use of panitumumab (Vectibix, Amgen) in RAS wild-type metastatic colorectal cancer is an example of the appropriate use of good evidence and regulatory authority. But, this general approach is likely only to be of true benefit if these new treatments are used as a replacement for less effective therapies, rather than simply shifting more traditional treatment options further down the therapeutic algorithm — adoption of the principles of the ASCO version of American Board of Internal Medicine’s Choosing Wisely campaign will be key.

The low genomic confidence that I feel in this area of somatic testing also applies to germline testing and issues of cancer susceptibility. Here again, my own knowledge base is lacking and there are plenty of data to show that many oncologists are in a similar position. Fortunately, this is an area in which genetic counselors are able to compensate for the knowledge gap of other providers, and it is also an area in which the value proposition should be easier to demonstrate — precision cancer screening and prevention in high-risk populations should be a highly effective strategy for reducing cost and improving outcomes.

The increasing prominence and marketing of personalized cancer care in the media is fueling higher patient expectations and challenging our ability as providers to stay on top of a rapidly growing body of knowledge. We should look to regulatory authorities to oversee the responsible marketing and application of these tests, and we should look to ourselves to generate the data that demonstrate the true value of individualized testing and treatment.

References:

Burton TM. Is Lab Testing the ‘Wild West’ of Medicine? The Wall Street Journal. Dec. 10, 2015. Available at: www.wsj.com/articles/is-lab-testing-the-wild-west-of-medicine-1449800707. Accessed Dec. 17, 2015.

Gray SW, et al. J Clin Oncol. 2014;doi:10.1200/JCO.2013.52.4298.

Gray SW, et al. J Natl Cancer Inst. 2015;doi:10.1093/jnci/djv030.

Mouchawar J, et al. Genet Med. 2005;7:191-197.

Schnipper LE, et al. J Clin Oncol. 2012;doi:10.1200/JCO.2012.42.8375.

For more information:

John Sweetenham, MD, is HemOnc Today’s Chief Medical Editor for Hematology. He also is senior director of clinical affairs and executive medical director at Huntsman Cancer Institute at the University of Utah. He can be reached at john.sweetenham@hci.utah.edu.

Disclosure: Sweetenham reports no relevant financial disclosures.

Almost every day my email and regular mail have at least one article related to the growth of precision cancer care; the promise of genomics and proteomics in identifying individualized, molecularly targeted therapies; and the use of real-time “big data” to inform treatment decisions for patients.

A few years back, these articles mostly appeared in peer-reviewed journals. That, of course, has changed. Although the peer-reviewed literature in this area continues to expand rapidly, I now receive information from other authoritative publications (such as HemOnc Today), as well as marketing materials from health care organizations and major cancer centers. I am also starting to see some commercial organizations increase their marketing of genomic products.

The excitement around the use of genomic and other tumor-derived data to allow for personalized cancer care is remarkable and completely justified — few of us doubt that these approaches will transform the care of cancer and many other diseases in the next few years.

Routine genomic testing

Along with this growing excitement, I sometimes feel some anxiety — and even insecurity — especially when I look at my colleagues in solid tumor oncology. For them, genomic testing and selection of molecularly targeted therapies based on these results is becoming relatively routine. In the lymphoma world, we have been somewhat behind the curve in this respect, although molecular subtyping of some lymphoma types will probably gain increasing clinical utility in the next few years. So, although I have a rudimentary understanding of the techniques, limitations and clinical utility of some of the somatic molecular analyses now available for our patients, my understanding of how my solid tumor colleagues apply these data in their clinical practice outside the trial setting and how these data influence outcomes is limited.

John Sweetenham, MD
John Sweetenham

I will be the first to acknowledge that my colleagues in solid tumor oncology — and, for that matter, in hematologic malignancy — are smarter than me, but I can gain some consolation in knowing that I am not alone. At least one study of oncologists’ attitudes and understanding of somatic genomic tests, conducted at a major NCI-designated cancer center, demonstrated a wide range of genomic knowledge, differing attitudes toward the disclosure of genomic information — especially if the significance is unknown — to patients, and uncertainty surrounding the clinical utility of these tests. Similar data have been reported from other studies of cancer specialists in academic and community settings, suggesting that a major knowledge gap may still exist.

It’s safe to assume that if there is a need for more education for those of us taking care of cancer patients, there is probably an opportunity to improve the information we provide to our patients and families, as well. This was brought home to me when I picked up on a recent article in The Wall Street Journal that labeled laboratory testing as the “‘Wild West’ of medicine.” The overall theme of the article was directed at a call for tighter regulation of lab-developed tests.

The article cited an excellent study recently published in Journal of the National Cancer Institute that explored the Internet marketing of personalized cancer care — specifically genomic testing — by for-profit companies, research institutes, academic cancer centers, hospitals and physician groups. These groups provide a range of services, including germline and somatic testing and, in some cases, interpretive services and personalized cancer care.

Several of the websites examined market-established tests that are backed by national guidelines, including testing for BRAF and EGFR, but overall, the websites were more likely to market nonstandard tests — more than 80% of all the sites that specified tumor testing identified nonstandard tests. Commercial websites were more likely than others to market chemotherapy-sensitivity testing and, of all the websites examined, 85% provided information about the benefits of genetic testing, whereas only 27% provided information on limitations of the techniques.

PAGE BREAK

The authors of this study also reported that few of the marketed somatic tests have been shown to have true clinical utility, and some of the sites offered tests that organizations such as ASCO have already concluded have insufficient evidence to support their use.

All of this is particularly sobering in the context of data that show direct-to-consumer marketing drives more patients to undergo genetic testing, even though many of them may not have the resources to interpret and understand the significance of the results. The evidence cited above suggests that they may not be able to rely on us, their oncologists, to give them reliable, fully informed guidance.

Reality gap

Tighter regulation could certainly go a long way toward limiting unnecessary and uninformative testing, but the spectrum of tests with proven clinical utility is likely to increase rapidly. Enhanced education of providers to raise their so-called “genomic confidence,” coupled with improved clinical decision support tools (of which many are now in various stages of development), will help to overcome the knowledge gap.

Overcoming the reality gap may be more challenging. As we embrace value-based cancer care, the true clinical impact of genomically driven treatment decisions will become a major determinant of the uptake of these tests. Some of the available genomic tests already have price points in excess of $10,000, and many of the molecularly targeted therapies cost more than (in some cases, much more than) $10,000 per month. Yet, for most, the clinical benefit appears to be limited to sometimes modest improvements in PFS, with no OS benefit and no suggestion that these treatments will be curative.

Hopefully, genomic testing will allow the use of these costly therapies to be limited to those patients most likely to derive benefit. If so, this should be a positive step toward delivering high-value cancer care. The recently updated FDA label for the use of panitumumab (Vectibix, Amgen) in RAS wild-type metastatic colorectal cancer is an example of the appropriate use of good evidence and regulatory authority. But, this general approach is likely only to be of true benefit if these new treatments are used as a replacement for less effective therapies, rather than simply shifting more traditional treatment options further down the therapeutic algorithm — adoption of the principles of the ASCO version of American Board of Internal Medicine’s Choosing Wisely campaign will be key.

The low genomic confidence that I feel in this area of somatic testing also applies to germline testing and issues of cancer susceptibility. Here again, my own knowledge base is lacking and there are plenty of data to show that many oncologists are in a similar position. Fortunately, this is an area in which genetic counselors are able to compensate for the knowledge gap of other providers, and it is also an area in which the value proposition should be easier to demonstrate — precision cancer screening and prevention in high-risk populations should be a highly effective strategy for reducing cost and improving outcomes.

The increasing prominence and marketing of personalized cancer care in the media is fueling higher patient expectations and challenging our ability as providers to stay on top of a rapidly growing body of knowledge. We should look to regulatory authorities to oversee the responsible marketing and application of these tests, and we should look to ourselves to generate the data that demonstrate the true value of individualized testing and treatment.

References:

Burton TM. Is Lab Testing the ‘Wild West’ of Medicine? The Wall Street Journal. Dec. 10, 2015. Available at: www.wsj.com/articles/is-lab-testing-the-wild-west-of-medicine-1449800707. Accessed Dec. 17, 2015.

Gray SW, et al. J Clin Oncol. 2014;doi:10.1200/JCO.2013.52.4298.

Gray SW, et al. J Natl Cancer Inst. 2015;doi:10.1093/jnci/djv030.

Mouchawar J, et al. Genet Med. 2005;7:191-197.

PAGE BREAK

Schnipper LE, et al. J Clin Oncol. 2012;doi:10.1200/JCO.2012.42.8375.

For more information:

John Sweetenham, MD, is HemOnc Today’s Chief Medical Editor for Hematology. He also is senior director of clinical affairs and executive medical director at Huntsman Cancer Institute at the University of Utah. He can be reached at john.sweetenham@hci.utah.edu.

Disclosure: Sweetenham reports no relevant financial disclosures.