NEW YORK – Precision oncology is based on the seemingly simple premise that cancer can be destroyed by identifying, targeting, and shutting down the molecular mechanisms driving it. In practice, cancer biology is far more complex, and targeting the mechanisms driving cancer is often elusive.
Although there have been remarkable success stories and more patients are getting genetic testing than ever before, advances in precision oncology have yet to benefit the majority of cancer patients. Looking to bridge this gap between promise and practice, a number of cancer centers and hospitals have invested heavily in precision oncology in recent years with the goal of advancing this still-burgeoning field.
In order to capture a snapshot of how precision oncology is being implemented today, Precision Oncology News surveyed 20 top US cancer centers and hospitals. We wanted to explore what types of molecular tests these centers offer, and when they are performed in the patient's cancer journey, what tools and expertise exist to help incorporate test results into guiding treatments and to what extent patients are enrolled in clinical trials investigating precision drugs.
The survey revealed that some investments, such as the ability to do in-house targeted next-generation sequencing panels, as well as germline and somatic testing, are nearly standard among surveyed cancer centers, many of which are early adopters of precision oncology approaches. However, there is still variability in other areas even among these early adopters. For example, not all cancer centers that practice precision oncology have implemented decision support systems to flag pertinent test results and help doctors personalize care for patients.
The survey also showed that these cancer centers face a multitude of challenges and that there is no standard metric by which they currently define the success of their precision oncology efforts.
In order to conduct this survey, we reached out to leaders of precision oncology programs at cancer centers around the country between April and July and asked them to answer an online questionnaire about these programs. Sixteen of the 20 respondents were employed at National Cancer Institute-designated cancer centers, and four were from large healthcare or hospital systems.
We targeted individuals at these institutions with specific knowledge of the resources available for personalizing cancer care, such as directors of precision medicine programs, heads of molecular testing labs, lead pathologists, and pharmacy specialists who help procure the medicines patients receive based on molecular profiling. The diversity of titles among respondents is a testament to the multidisciplinary expertise necessary to deliver precision cancer care.
The questions in the first part of the survey aimed to assess the types of molecular testing available at cancer centers and hospitals, since precision treatment can only happen after understanding the biological features of patients' disease. All responding centers offer a broad testing menu. More than half of those surveyed indicated they perform single-gene testing in house, while half are internally conducting RNA sequencing and assessment of biomarkers for personalizing immunotherapy treatments, and eight indicated they use in-house targeted NGS panels. Respondents were much more likely to outsource liquid biopsy testing as well as whole-genome or exome sequencing than to run these tests in house.
The survey showed that institutions are investing in biomarker testing to personalize immunotherapies, such as pembrolizumab (Merck's Keytruda) and nivolumab (Bristol-Myers Squibb's Opdivo), recognizing that only an estimated 20 percent of cancer patients have a durable response to these types of drugs and there is a need to identify best responders. Although current immunotherapy biomarkers, such as PD-L1 expression and tumor mutational burden, don't perfectly discriminate between responders and non-responders, the majority of surveyed institutions have access to tests for these markers, either internally or through commercial labs.
Additionally, research has shown that in order to accurately characterize the mechanisms that are truly driving disease, molecular features of patients' cancer cells must be considered against the characteristics of normal cells. Therefore, it is encouraging that 90 percent, or 18 of the surveyed institutions, indicated they perform somatic and germline testing, while two institutions perform somatic testing only.
Once testing is performed, however, the results must be evaluated to determine what treatment course to take and incorporated into physician workflows, all of which requires further investment into forming multidisciplinary expert teams and electronic decision support systems. Given the complexity and length of reports coming out of NGS panels that gauge hundreds of genes, it's perhaps no surprise that 80 percent of institutions said they convene molecular tumor boards that meet regularly to discuss patient cases. All those surveyed said they employed genetic counselors, who in recent years have become important members of precision care teams given their critical role in explaining test reports and treatment options to patients.
Beyond human expertise, true integration of precision oncology into mainstream medicine requires investments to incorporate patients' test results into electronic medical records for informing future care. While all the responding institutions said that genetic test results end up in patients' EMRs in some manner, 45 percent indicated that they don't have decision support tools in place so doctors can access relevant genomic information when they need it in patient care.
Although our survey clearly indicates that cancer centers around the country are making the necessary investments to be able to deliver precision oncology, the success of these programs in terms of the impact on patients is obfuscated by the lack of systems for tracking outcomes or standard metrics for measuring them. In our survey, 30 percent, or six institutions, indicated they had no system in place for tracking patient outcomes after receiving molecularly informed treatment.
Although 70 percent of responding institutions do have a system in place for tracking outcomes, they cited a variety of methods for doing so. Several respondents reported that patient outcomes are tracked within individual clinical trials, but there is no institution-wide outcomes-tracking system for those receiving precision treatments outside of these studies. Others said outcomes are collected via clinical follow up and chart review, through EMR data mining, and one respondent indicated working with health technology firm Flatiron Health.
When we asked respondents to describe the metrics by which their precision oncology programs measured success, the most common answer was the number of patients molecularly matched to clinical trials. This aligns with the fact that clinical trials are a major feature of precision oncology programs at the institutions represented in our survey. All institutions represented in the survey are conducting precision oncology clinical trials (those involving biomarkers or that feature basket or umbrella designs), while 85 percent of respondents stated that their cancer centers could also enroll patients in external studies investigating precision oncology approaches.
However, if clinical trial enrollment is the main measure of success for these programs, then the survey shows there's a lot of room for improvement, since almost half reported that less than 10 percent of patients are matched to studies based on molecular markers, and a quarter of respondents reported a match rate of between 10 percent and 20 percent.
Precision oncology proponents have pointed out that the match rate is low because patients are generally offered the chance to enroll in these studies only as a last option, when they are nearing the end of their battle with cancer. Many patients succumb to their disease before molecular test results come back, or while the logistics of trial enrollment and drug access issues are being addressed. Experts in the field believe that patients may have a much better chance of not only matching to precision oncology trials but benefitting from molecularly guided treatments if they are tested and treated in earlier stages of disease.
According to our survey, this is starting to happen. Nearly half of the respondents indicated that they offer molecular testing to inform precision treatments only to cancer patients who have Stage III, IV, or advanced disease. However, eight institutions, or 42 percent, indicated they offered testing to Stage I patients, and 11 percent said they begin offering testing to patients at Stage II.
After clinical trial enrollment, the second most cited success metrics were testing volumes and publication rates, while cost effectiveness and patient outcomes (i.e. response, progression-free survival, overall survival) tied for third most mentioned. Two respondents said that success metrics at their institutions were "to be decided" and "in development." Only one mentioned the number of US Food and Drug Administration-approved drugs based on trials initiated at the institution as a measure of precision oncology success.
As to the challenges institutions face in being able to deliver precision oncology, half mentioned reimbursement or funding, one-fifth noted physician education or adoption as a hindrance, 15 percent indicated clinical trial access, and the same proportion mentioned IT or data challenges.
Our findings are in line with results that other surveys of this type have reported. In 2015, Kurzrock et al. published a survey of 24 National Comprehensive Cancer Network member institutions and eight affiliate sites, and reported that all the respondents' institutions were using molecular profiling to inform patient care. Respondents to this survey also cited reimbursement and access to drugs on and off clinical trials as a major barriers to integrating molecular testing into patient care.
Another survey of more than 1,200 oncologists by Freedman et al. published in 2017 indicated that NGS uptake was on the rise, with 75 percent reporting they used results from such tests to guide patient care. This survey showed there was greater use of NGS testing among oncologists who had access to a molecular tumor board and for patients with advanced refractory disease, which corroborates our findings.
At the American Society of Clinical Oncology's annual meeting this year, Schilsky et al. reported on a survey of more than 100 physicians at sites participating in the Targeted Agent and Profiling Utilization Registry (TAPUR) basket trial, which is exploring off-label uses of already approved drugs in patients with specific tumor markers. Like our survey, this one showed that while most doctors ordered genomic testing in patients with advanced disease, around a third indicated their willingness to order testing for those with earlier stage cancers.
The Precision Oncology News survey aimed to assess current practices among organizations that are currently implementing these approaches — many of which are well-funded research centers that have helped to pioneer the field — so it likely does not fully capture the challenges of implementing precision oncology at more under-resourced, community, or rural cancer centers. Nevertheless, we believe the results provide a fair snapshot of what precision oncology looks like in practice today and could serve as an initial benchmark for healthcare systems looking to implement their own precision oncology programs.
We'd like your feedback! Precision Oncology News hopes to conduct this survey annually. Please contact Turna Ray if you'd be interested in participating in next year's survey or if you have ideas for additional questions.