NEW YORK – Cancer centers and health systems in the US continue to invest in molecular testing, decision support, and other tools for personalizing treatment, but have yet to establish clear metrics for evaluating the extent to which these approaches are benefitting patients, according to a recent survey.
Precision Oncology News queried experts within precision oncology programs at 21 US cancer centers and hospitals to explore the types of resources oncologists have access to for personalizing cancer care; how these programs are measuring the impact of these interventions on patients; and how the pandemic has affected key aspects of these programs, such as access to genomic testing and clinical trial enrollment.
This second annual precision oncology survey, conducted between May and October 2020, showed, as the 2019 survey did, that in-house single-gene testing and targeted next-generation sequencing panels are now widely available within large institutions. However, this year's survey presented a unique opportunity to capture how the COVID-19 pandemic has, at least temporarily, disrupted providers' ability to fully marshal those resources for patient care.
A necessary first step in precision oncology is genomic testing of cancer patients for targetable tumor markers. Surveyed providers at major cancer centers and hospitals indicated they had access to a wide range of biomarker assessment tools, either through internal labs or commercial testing firms. For example, all respondents indicated that their institutions' in-house labs had the ability to test cancer patients for single oncogenes; 80 percent said they had access to in-house targeted NGS panels and tests for immunotherapy biomarkers; and nearly 70 percent said they had internal RNA sequencing capabilities.
Although some providers at institutions with internal NGS panels also order such tests from commercial labs, programs are more likely to outsource liquid biopsy testing, exome sequencing, and whole-genome sequencing. When asked to identify the commercial labs they order tests from, respondents most frequently mentioned Roche subsidiary Foundation Medicine, which markets tissue and liquid biopsy NGS panels approved by the US Food and Drug Administration. The second most frequently mentioned commercial lab was Guardant Health, which also recently achieved FDA approval for its Guardant360 liquid biopsy NGS test, followed by Caris Life Sciences, and Tempus. These were also the most frequently mentioned labs for send-out testing in 2019.
Last year's survey indicated that institutions were investing in biomarker testing to personalize immunotherapies, and unsurprisingly, that trend has continued this year as the FDA has approved more immunotherapy indications reliant on PD-L1 expression status, microsatellite instability, and mismatch repair deficiency. During the course of the 2020 survey, the agency also approved a second tissue-agnostic indication for pembrolizumab (Merck's Keytruda), which means that patients with any kind of refractory solid tumor can now be eligible for the immunotherapy based on three biomarkers: high tumor mutational burden, high microsatellite instability, or mismatch repair deficiency.
Almost all those surveyed said that cancer patients considering immunotherapy at their institutions are tested for PD-L1 expression; three-quarters said patients are assessed for microsatellite instability; two-thirds noted patients are evaluated for tumor mutational burden; and one-fifth indicated performing immunohistochemistry to assess patients' mismatch repair status.
Hurdles to treatment
In order to deliver precision cancer care, it's not enough to just order genomic testing, but oncologists must distill clinically actionable information from patients' test reports and use it to guide their treatment. However, the report may not contain any "actionable" biomarkers, and even when it does, there may not be any FDA-approved treatments associated with the detected biomarkers. Although the FDA is approving more molecularly informed cancer drugs every year, the best options for precision therapy for many patients are off-label treatments or investigational drugs within clinical trials, often based on emerging or limited evidence that the molecularly guided approach might benefit them.
Assessing this evidence and identifying precision treatment opportunities remain a challenge for oncologists. Toward that end, all 21 survey respondents indicated that their institutions have biomarker-guided drug trials, basket trials, and umbrella studies that patients can enroll in if they fit inclusion and exclusion criteria, and 90 percent said they are able to enroll patients into precision oncology trials at external sites.
Despite the availability of trials, however, only a minority of patients enroll in them. Nearly three-quarters of surveyed experts (72 percent) indicated that 20 percent or fewer cancer patients at their institutions are enrolled in a precision oncology trial based on their molecular test results. Experts from only two institutions estimated that more than 50 percent of molecularly profiled patients matched to a clinical trial.
The enrollment rates captured in this survey are in line with what other precision oncology studies have reported. For example, recently published data from the National Cancer Institute's Molecular Analysis for Therapy Choice (MATCH) trial revealed that around 12 percent of approximately 5,500 sequenced cancer patients received treatment in a study subprotocol based on their tumor markers.
A major reason for the low match rate in precision oncology studies is that there simply aren't treatments that can target the majority of rare genomic alterations detected in patients' tumors. Even if a tumor marker is deemed therapeutically "targetable," often there isn't enough evidence to reasonably suspect that the drug will benefit patients with a particular mutation. And when there is some evidence to reasonably hypothesize that certain molecularly driven tumors might respond to specific drugs, by the time many patients get tested, their cancers are too advanced and they no longer qualify for the study.
This year's survey, like last year, suggested that at least at some institutions, patients are being genomically profiled earlier in their disease trajectory to avoid this last pitfall. Only two experts noted stage IV disease as the earliest time when patients are offered testing, while five, six, and eight respondents indicated that their institutions are molecularly profiling patients with stage I, II, and III disease, respectively.
Additional resources, such as electronic medical records containing patients' test reports, decision support alerting doctors to actionable results, and a molecular tumor board of genomics experts, can also help oncologists identify opportunities for precision treatment. This year, 100 percent of respondents said that genetic test results are incorporated into patients' electronic medical records. Around 60 percent said their institutions have decision support tools to help doctors make sense of test results at the point of care.
Several respondents wrote in that they have access to molecular tumor boards where experts discuss what action may be taken for patients based on their cancer markers. One expert from an academic cancer center in the Midwest noted that oncologists in the region have access to a state-funded molecular tumor board, suggesting growing recognition, beyond early adopter circles, of precision oncology as part of standard cancer care.
What is 'success'?
The surveys from this and last year clearly show continued adoption of genomic testing at cancer centers around the country and acceptance of the idea that every cancer patient should have the opportunity to be evaluated for precision treatment. However, there is also an increasingly vocal group of oncologists who counter that the push to broaden access to precision oncology is largely based on hope and hype rather than actual evidence that molecularly informed treatment strategies are helping most cancer patients live longer and better lives.
In order to demonstrate the value of precision oncology programs, cancer centers will need to track patients' outcomes on molecularly informed treatment strategies. In the 2020 survey, 9 percent of respondents said that they did not track patients' outcomes once they are on a molecularly guided treatment strategy. Meanwhile, 9 percent indicated their institutions only recorded patients' outcomes within individual clinical trials, another 10 percent said they sift through electronic medical records for outcomes information, 5 percent collect this information via clinical follow up and chart review, and 57 percent indicated they do a combination of these various approaches.
Moreover, when asked what metrics their institutions use to gauge the success of precision oncology programs, eight out of 21 experts did not answer. Of the 13 who did, respondents commonly mentioned the proportion of cancer patients receiving genomic testing as a measure of success, and the number of patients enrolled in trials or receiving treatment based on test results. Only four respondents mentioned patients' outcomes on the molecularly informed treatments they received as a factor to consider when assessing the success of precision oncology programs.
This may be a reflection of the fact that precision oncology is still a relatively new discipline in cancer care. These programs are difficult to set up and face significant implementation hurdles. When queried about the challenges to implementing precision oncology at their institutions, respondents identified data analysis (20 percent), clinical trial access (15 percent), and physician education or adoption (15 percent). However, the biggest barrier, cited by 30 percent of experts, was reimbursement or funding, as was the case in 2019, when 50 percent of respondents marked this as their most persistent headache.
Amid a pandemic
During 2020, the COVID-19 pandemic has presented a unique difficulty for the timely diagnosis and treatment of cancer patients, who are among the most vulnerable to SARS-CoV-2 infection. Half the survey respondents said that diagnosis of new cancer patients dropped by 10 percent to 25 percent at their institutions due to pandemic restrictions, while one-fifth said new diagnoses decreased by less than 10 percent, and only one-tenth said they saw no impact on the diagnosis of new patients as a result of the pandemic.
The pandemic also placed pressure on certain aspects of precision oncology programs, such as the ability to molecularly profile cancer patients and conduct clinical trials. In the survey, 55 percent said the pandemic did not impact their ability to molecularly profile cancer patients. However, 36 percent said that their institutions experienced temporary delays in getting test results back at the start of the pandemic, though turnaround times eventually returned to normal. Meanwhile, 9 percent said that they experienced delays in receiving test results and expect the delays to continue for some weeks or months.
The impact of the pandemic on cancer patients' ability to access drug trials is a particularly important metric given this is often the only avenue through which patients can access investigational precision oncology treatments. Although many cancer centers and hospitals in recent months have implemented telemedicine and remote monitoring approaches to try to diminish disruptions to ongoing clinical trials, more than 60 percent of respondents indicated that the pandemic affected their institutions' ability to enroll patients into studies.
Two respondents in early May indicated that enrollment in all drug trials at their institutions were on hold. However, experts who completed the survey in subsequent months indicated that earlier in the pandemic their institutions had temporarily halted enrollment or other aspects of studies, including precision oncology studies involving sequencing, but suggested that things were returning to normal.
In conducting this survey, Precision Oncology News reached out to National Cancer Institute-designated cancer centers and regional hospitals around the country. The 21 respondents are from institutions distributed throughout all regions of the US, but include organizations that have made some, if not significant, investments in precision oncology. As such, the challenges identified in this survey are likely more pronounced within community practices with limited resources to put toward in-house genomic testing capabilities, clinical trial enrollment, decision support tools, molecular tumor boards, and outcomes tracking.
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