There is general agreement that the eligibility criteria in cancer clinical trials need to be broadened. Doing so would not only increase the number of patients enrolled in protocol-driven, investigational treatment plans, but also improve the generalizability of results.

In 2021, ASCO and Friends of Cancer Research published recommendations for broadening the eligibility criteria for cancer trial participation. Earlier this year, in a study presented at the Genitourinary Cancers Symposium, a review of 205 advanced urothelial cancer (aUC) trials with start dates between 2012 and 2022 showed that a “modest percentage” used overly restrictive eligibility criteria for enrollment. Daniela V. Castro, MD, of City of Hope Comprehensive Cancer Center in Duarte, California, and colleagues found that the most common exclusion criterion was HIV positivity.

The researchers found that in spite of limited evidence for any significant impact on drug efficacy and tolerability, HIV positivity was used as an exclusion criterion in 89.2% of 37 studies with publicly accessible data. Thirteen of these trials evaluated combination therapy, 11 evaluated immunotherapy, eight assessed targeted therapy, and five looked at chemotherapy.

“While eligibility criteria intend to prioritize patient safety and define a specific study population, these criteria are often based on outdated standards and may not be reflective of real-world practice,” the authors wrote. “Reassessing and updating eligibility criteria will ensure that the resulting data is more reflective and inclusive of a real-world population.”

Notably, the use of HIV positivity as an exclusion criterion in the trials was significantly associated with the class of therapy. This was identified in 100% of trials evaluating combination therapy and immunotherapy, and in 87.5% of targeted therapy trials compared with 40% of chemotherapy trials. In contrast, HBV/HCV positivity, brain metastases, and concurrent malignancies were used as exclusion criteria independent of treatment class, in 56.8%, 35.1%, and 5.4% of studies, respectively.

In the following interview, co-author Abhishek Tripathi, MD, also of City of Hope Comprehensive Cancer Center, discussed the findings in greater detail.

Were there any unexpected findings?

Tripathi: Yes, indeed, one finding caught us off guard. Overall, we observed significantly fewer therapeutic clinical trials available to patients with advanced urothelial cancer compared to some of the other malignancies. This highlights an unmet need for patients with this disease.

Why is it crucial that eligibility criteria in aUC trials reflect real-world practice?

Tripathi: Patients in clinical practice frequently present with more complex comorbidities than those seen in typical aUC clinical trial cohorts. Since these factors significantly influence treatment outcomes, eligibility criteria that reflects real-world experience play a vital role. It is imperative that we ensure that our clinical trial patient population reflects the real world as much as possible.

Our study underscores the need for a shift in how we design clinical trials, particularly in the direction of expanding eligibility criteria.

What potential impact might broader eligibility criteria have?

Tripathi: The expansion of eligibility criteria for clinical trials would enhance the relevance and accuracy of the data collected. The inclusion of patients currently facing barriers to clinical trial enrollment could also stimulate the investigation of treatment strategies more likely to be applicable, tolerable, and effective in this population, and thereby have wider implications for the treatment of disease overall.

What barriers remain?

Tripathi: In our view, it is likely that multiple factors contribute to the persistent use of outdated standards for clinical trial enrolment. Chief among them is patient safety. For example, patients with diseases such as HIV and hepatitis C were historically excluded from participating in clinical trials. Since treatment advances means these patients can now achieve normal or near-normal immune function, they should be considered for clinical trial enrollment.

What is your main take-home message for physicians?

Tripathi: Strive for more inclusivity when recruiting patients for clinical trials.

What’s next for your research?

Tripathi: We are currently planning a study to investigate the potential socioeconomic barriers to clinical trial enrollment.

Read the study here.

https://www.medpagetoday.com/reading-room/asco/bladder-cancer/105253