In a provocative new report, the chief medical officer (CMO) of England has called for all patients with cancer, as well as those with rare diseases, to undergo full genomic sequencing.
In fact, genomic sequencing should become part of routine medical practice for these patients and be as standard as blood tests and biopsies.
"Please, can we move from talking and experimenting about genomes and move it into practice for patients," said CMO Dame Sally Claire Davies, DBE, FMedSci, FRS, in an interview with The Telegraph.
In her report, which is compiled independently and without government input, Dr Davies says that genomic medicine has the potential to "save costs and improve quality of care by targeting treatment, maximizing benefit and reducing side effects."
This is particularly true for patients with rare diseases, who often undergo a lengthy "diagnostic odyssey." Genomic sequencing can potentially provide a more rapid diagnosis, identify therapeutic options faster, and improve outcomes.
"By moving from a cottage industry and into modern science, not only do we bring it much closer to patients, but we will get more bang for our buck," said Dr Davies. "We need to develop a genomic literate set of professionals, both doctors and nurses and even managers, so that they walk with us into this new era."
Every patient gets their genome done if they've got cancer. Dr Sally Claire Davies
Dr Davies emphasized that she would like all "appropriate patients to get the opportunity. My dream is in the end that every patient gets their genome done if they've got cancer."
The leading UK cancer charity, Cancer Research UK, reacted with enthusiasm to the announcement. Sir Harpal Kumar, chief executive of Cancer Research UK, statedthat "This timely report from the chief medical officer showcases just how much is now possible in genomics research and care within the NHS [National Health Service]."
However, two US experts approached for comment were both critical of the proposal.
Widespread genomic tests of patients with cancer offers up the promise of "precision oncology" of matching treatments to specific mutations, with the premise that this will be a more effective therapy and improve response and outcomes.
But thus far, precision oncology has not been shown to work, and the data are just not there, commented Vinay Prasad, MD, MPH, a hematologist-oncologist at the Knight Cancer Institute, Oregon Health and Science University, Portland.
It's a very foolish thing to suggest testing all patients at this juncture, because it is abundantly clear we are not there yet," Dr Prasad told Medscape Medical News. "It's not even being done at tertiary cancer centers in the US, which are often on the cutting edge."
For them to go ahead with this seems a little bit reckless. Dr Vinay Prasad
In contrast, the United Kingdom is generally far more thoughtful and careful as to how they fund cancer care, he pointed out. "For them to go ahead with this seems a little bit reckless."
Dr. Prasad emphasized that to date, there is a lack of data from phase 3 randomized trials comparing patients who undergo genomic testing and then receive tailored treatment based on those results vs patients who receive standard therapy.
"And then we would need to see a survival benefit in the patients who did receive the tailored treatment," he said.
Dr Prasad pointed to the MOSCATO trial, which used genomic testing to select treatment for patients. Although this was not a randomized trial, the results showed the limitations of testing.
After patients received a targeted therapy based on genetic testing, the overall response rate was 11%, with 2 patients achieving a complete response and 20 patients showing a partial response. In addition, 100 had stable disease and 33 had progressive disease. The median overall survival duration was 11.9 months.
An actionable molecular alteration was identified in 411 of 843 patients, but only 7% actually benefited from this strategy, Dr Prasad pointed out.
A similar trial, the ProfiLER study, presented at this year's annual meeting of the American Society of Clinical Oncology (ASCO) and reported by Medscape Medical News at that time, also showed limited results.
Among patients who had at least one "actionable" alteration (52% of 2676 enrolled) and who received recommended targeted therapy, 53.7% were alive after 3 years, as compared with 46.1% of patients who did not.
The 5-year survival rate was also higher for patients who were treated with a targeted agent (34.8% vs 28.1%).
Richard Schilsky, MD, chief medical officer at ASCO, found the study to be somewhat "disappointing."
"This study is similar to what many other studies are showing ― the researchers found an actionable mutation in about 50% of patients, which is similar to what other groups have reported in the same ballpark, and then targeted therapy available for about 35% of them," he commented during the meeting.
This translated to only about 100 patients who were able to receive the targeted therapy, with a median progression-free survival duration of 2.8 months, he pointed out. "So your view of these results depends on whether you are a glass-half-full or a glass-half-empty person — 5% to 10% of patients who get the drug respond, but these responses are relatively short-lived," he said.
"Little More Than a Lottery"
Dr Prasad also noted that next-generation sequencing is very expensive and could cost hundreds of millions of dollars to test every patient with cancer in the United Kingdom. "And it is not clear that this information will necessarily lead to better choices," he said.
It is particular interesting that England should go for this because the health system has refused to pay for cancer drugs that are effective but now appears to be willing to shoulder the cost for widespread genomic testing.
I consider this an inappropriate recommendation. Dr Jack West
Another US expert agrees. "Based on the absence of prospective population data, I consider this an inappropriate recommendation, and ironic that it is coming from a system that has decided it cannot cover interventions with a proven survival benefit because of concerns that they are not sufficiently cost-effective," commented Jack West, MD, medical oncologist and chair of the Outreach, Education, and Telemedicine Workgroup at Providence/Swedish Health & Services, Seattle, Washington.
"It is unfortunate to forgo treatments with a proven benefit in favor of interventions with no proven improvement in population-based cancer outcomes, seemingly based more on newsworthiness than proven benefit," Dr West told Medscape Medical News.
"I also think it's likely to prove very frustrating to have a large number of patients for whom a potentially or known effective treatment is identified but will not be covered in the UK," he added.
Dr West pointed out that it could be a great opportunity to facilitate targeted therapy research if patients with an identified marker for which there is an investigational agent have access to clinical trials with those agents. "If such research opportunities are not available, however, I fear it is likely that a policy of broad genomic testing is more likely to escalate only frustration and costs, without a demonstrable improvement in outcomes for cancer patients," he said.
Given the current level of data, which consist primarily of retrospective data and anecdotal reports of "remarkable results" for selected patients with uncommon to rare mutations, a policy of favoring "broad molecular testing for all cancer patients is little more than a lottery, with highly visible winners, but far more who end up losing," Dr West added.
Report Urges Widespread Genomic Testing
The report outlines a lengthy list of goals and recommendations for making widespread genomic testing a reality, while at the same time making sure that patient privacy is protected.
One recommendation is to centralize genetic testing of patients in the NHS and set up a national network. This would make the process more standardized and ensure that all patients had equal access to testing. Currently, genetic testing is conducted at 25 regional laboratories and several smaller centers.
Another is to set up a new National Genomics Board, which would oversee the expansion and development of genomic services.
The establishment of genetic testing would likely make cancer screening programs more effective by targeting the screening at individuals who are most likely to benefit and least likely to be harmed, the report suggests. Screening for breast, prostate, colorectal, and lung cancer provides the most immediate opportunities, it adds.
Dr Davies does acknowledge that patients will have concerns about privacy and the protection of their personal data and that they may struggle to grasp the full concept of what genetic testing can accomplish. "The field of genomics is complex, and we cannot expect patients to understand it readily," she writes. "As members of clinical teams we must engage patients and the public and develop real partnerships."
Key to this process is having a short, simple, understandable, and workable consent process for patients to choose how confidential genomic data about them are used.
The report also highlights gaps in infrastructure, public engagement, organization of research, and provision of services that need to be addressed in order to implement the proposed policies.