Patients With Comorbid Conditions Still Can Benefit From Clinical Trials

Ellie Leick

In some cases, patients with cancer who are rejected from clinical trials because they are "too sick," are the patients who would benefit the most from the trial.

Many patients with a poor cancer prognosis often get turned away from participating in clinical trials because they are deemed “too sick” according to eligibility criteria, yet many who are being turned away are those who could benefit the most from enrolling in a clinical trial.

A recent novel study at the University of Texas MD Anderson Cancer Center showed patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) responded well and were safely treated in a clinical trial setting, though they would not typically qualify.

According to lead author Guillermo Garcia-Manero, MD, Professor of Leukemia at the MD Anderson Cancer Center, the most common reasons why patients are excluded from clinical trials are their poor kidney function, poor liver function, malignancy, and life expectancy. Garcia-Manero, a professor in the Department of Leukemia at MD Anderson, added that there is often no clinical reason for patients with these comorbidities to be excluded:

“Clinical trials are meant to protect the patient, however, the eligibility criteria in place protects the study rather than the patient.”

The study followed 109 patients with AML and MDS who were aged at least 17 years old and had not previously received treatment for AML or MDS. All participants had poor performance, organ dysfunction, or comorbidities. The main endpoint of the study was 60-day survival.

The trial began with 30 patients, including 16 patients with MDS and 14 with AML, and they were treated with azacitidine and vorinostat. The 60-day survival rate for this initial cohort was 83%. Adverse events that were observed involved mostly low-grade gastrointestinal (GI) side effects. When the study expanded to include 79 more patients, the 60-day survival rate was 79% with, once again, reports of low-grade GI side effects and a median overall survival (OS) of 7.6 months and event-free survival of 4.5 months. Median overall and event-free rates ere, respectively.

During the trial, there were “stopping rules” that required physicians to monitor the patients’ side effects and complete response rates. If a patient’s reaction did not indicate there would be a complete response within a 60-day period, they were immediately taken off and placed on another therapy. Researchers relied on previous data of 181 patients treated at MD Anderson when creating the minimum expected survival and response rates.

The study opens this issue up to further evaluations regarding the eligibility criteria with potential for allowing more people to be eligible for clinical studies: “I want to bring attention to this research,” Garcia-Manero said. “Exclusion from clinical trials happens in many diseases so this research is relevant to many people.”

Montalban-Bravo G, Huang X, Jabbour E, et al. A clinical trial for patients with acute myeloid leukemia or myelodysplastic syndromes not eligible for standard clinical trials. Leukemia. DOI: 10.1038/leu.2016.303.