“You can start with NCCN,” Dr Prasad asserted. “But then you need to know the data. [Are they] good data; credible data?” At minimum, Dr Prasad said, doctors should discuss the research findings with the patient and alert them to any uncertainty involving the study conclusions.
Dr Prasad, a frequent critic of the cost-effectiveness of some cancer drugs, noted that some guideline authors might be influenced by financial conflicts of interest, which could introduce bias into the guideline creation process. He cited a 2016 JAMA Oncology study, which found that 108 of 125 NCCN authors had reported at least 1 financial conflict of interest during 2014.4 On average, the authors received slightly more than $10,000 in a single year in general payments, including fees for consulting, food, and gifts; and approximately $236,000 in research-related payments, including funding associated with clinical trials.
Off-label prescribing has always been an option once the doctor has exhausted standard treatment options, Dr Schilsky said. But the difference is that today’s genetic testing can flag a particular mutation, raising patient expectations and fueling “greater hope that the treatment will work,” he said.
“But what we’ve come to recognize, of course, is that not all of these genomic abnormalities carry the same consequence in every kind of cancer,” Dr Schilsky remarked. Moreover, he said, because off-label prescribing decisions are typically made on a one-off basis, much of the information about whether the treatment conferred a clinical benefit in the particular off-label setting under investigation may not be properly tracked nor shared widely among oncologists.
In 2016, ASCO leaders launched (and are sponsoring) the Targeted Agent and Profiling Utilization Registry (TAPUR) study, which, as of late fall 2018, had enrolled nearly 1200 patients whom had both an advanced cancer and a potentially actionable genetic alteration, according to Dr Schilsky.5.6 To be included in the trial, the patient’s tumor variant had to be a known drug target or a validated drug-sensitivity biomarker.
The purpose of the multicohort, prospective, nonrandomized clinical study is to match commercially available targeted therapies to patient tumor biomarkers, as well as to determine the activity of various targeted therapies when they are used in an off-label setting.