Study findings point to “a concept that has haunted clinical trialists for years,” says one expert.
Researchers have found that real-world metastatic renal cell cancer patients being treated with tyrosine kinase inhibitors are often sicker than subjects in clinical trials for these drugs, leading to questions about safety for use in the very patients who need the drugs in clinical practice.
In fact, 39% of real-world patients are ineligible for pivotal clinical trials for tyrosine kinase inhibitors, according to a study published online in the Journal of Oncology Practice (Sept. 1, 2015).
A urologic cancer expert told Urology Times that the problem identified by this study doesn’t just apply to kidney cancer trials.
The study’s authors compared baseline characteristics of metastatic renal cell cancer patients in phase III clinical trials for four drugs recently FDA approved for kidney cancer treatment with real-world patient characteristics in a retrospective registry composed of academic and community practices.
“We found that patients participating in clinical trials are younger and healthier than many of the patients who are receiving these drugs in the clinical setting,” said lead author Aaron Mitchell, MD, of the University of North Carolina Medical Center, Chapel Hill, in a press release from that institution. “If a person will be getting the drugs in a clinical setting, it is important to know if they can expect to see the same benefits or if they might experience more dangerous side effects. Physicians can’t know for sure because the trial data do not directly apply.”
It shouldn’t be physicians’ responsibility to analyze how trial data might impact real-world patients. Rather, clinical trials should be more inclusive, Dr. Mitchell said. That’s easier said than done, however. Enrolling sicker patients will make the drug trials more expensive. A more realistic solution might be to change the perception that FDA approval is the endpoint for studying a drug’s effectiveness and continue with additional post-marketing data collection and analysis, according to Dr. Mitchell, who worked on the study with Bradford Hirsch, MD, and colleagues.
This problem is not limited to kidney cancer trials. Traditional criteria for trials include exclusion of patients who may not be considered the best candidates, according to Urology Times Editorial Council member Leonard G. Gomella, MD, of Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia.
“The authors have revisited a concept that has haunted clinical trialists for years, namely, that clinical trial participants may not be representative of the ‘real-world’ patients that will ultimately take these new cancer medications. This group of patients may be sicker, older, and suffer from comorbidities that may have been exclusions for trial enrollment,” Dr. Gomella told Urology Times.
“The use of post-approval phase IV or registry data combined with the advances in pharmacogenomics may potentially identify the best responders beyond traditional clinical parameters and may offer a solution for future trial design. Urologists who choose to administer these new cancer medications should be intimately aware of the subtleties between the patients they treat and the clinical trial parameters that led to the drugs’ approval to minimize any avoidable adverse outcomes,” added Dr. Gomella, who was not involved with the study.
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