Researchers: Mesothelioma Trials Need More Inclusive Criteria
February 2, 2021
“A broader patient population more resembling real life would be able to access the novel treatment early,” Dr. Steven Kao, medical oncologist at Chris O’Brien Lifehouse hospital and one of the study authors, told The Mesothelioma Center at Asbestos.com. “And when the trial results are published, the efficacy results would be more applicable to the real-world population.”
Clinical Lung Cancer published the study in 2020, accentuating the high rates of ineligibility caused by criteria that is too strict, potentially denying many patients the chance for improved mesothelioma survival.
Authors were from the University of Sydney Medical School and the Chris O’Brien Lifehouse Department of Medical Oncology.
The retrospective study ran from 2012 to 2018 and involved 133 consecutive patients with unresectable malignant pleural mesothelioma. All attended the medical oncology clinic at Royal Prince Alfred or Chris O’Brien Lifehouse hospitals in Sydney.
Qualifying for Mesothelioma Clinical Trials Is Difficult
Data for the study was compared to eligibility criteria for the international MAPS and KEYNOTE-028 studies, involving immunotherapy agents bevacizumab and pembrolizumab in combination with chemotherapy.
Of patients treated at one of the two leading centers in Australia, 50.5% failed to meet the eligibility criteria for the MAPS trial and 37% failed to qualify for the KEYNOTE-028 study.
Age (under 75) and performance status (Eastern Cooperative Oncology Group Scale) were the two most restrictive factors for patients not meeting the eligibility criteria. Others included concomitant medication and comorbidity.
In the MAPS clinical trial, median overall survival for those eligible was 25.1 months, compared to 21.5 months for those not eligible.
With the KEYNOTE-028 clinical trial, the median overall survival was 25.1 months for those eligible and 19.5 months for those ineligible.
“Clinicians should think about whether the particular treatment in question would result in similar efficacy or toxicity if their patients don’t fit in the eligibility criteria,” Kao said. “It is important to recognize that and discuss with patients accordingly.”
Investigational Drugs Benefit Mesothelioma Patients
Although efforts to broaden eligibility criteria for all clinical trials is ongoing – an estimated 10% of cancer patients overall participate in clinical trials, according to the study – limited participation makes advancements more difficult.
In this retrospective study, the majority of those who were eligible for the MAPS and KEYNOTE-028 trials did not participate in either trial. Of the 26.3% who were part of an investigational anticancer therapy study, the median overall survival was 32.4 months, compared to just 20.5 months for those who did not participate.
The issue of restricting eligibility is especially critical in rare cancers such as mesothelioma, presenting a barrier to efficient drug treatment development.
“This work is hypothesis generating,” the authors wrote. “Perhaps these exclusion criteria could be relaxed in future trials of patients with malignant pleural mesothelioma, although future study is warranted.”
The U.S. Food and Drug Administration approved the immunotherapy combination of Opdivo and Yervoy, known generically as nivolumab and ipilimumab, for first-line treatment of unresectable pleural mesothelioma in October 2020. It was the first new drug regimen approved in 16 years.
In July 2020, the FDA approved Keytruda, also known as pembrolizumab, in limited use for metastatic tumors, but only with certain restrictions for pleural mesothelioma.
“We have established that the MAPS and KEYNOTE-028 trials in MPM enrolled a select population that differs greatly from regular patients seen in the clinic,” the authors wrote. “This finding presents a challenge in practicing truly evidence-based medicine for real-world cohorts.”
The overall median survival was 22.7 months when all 133 patients were grouped, considerably better than the average survival for patients diagnosed with mesothelioma today.
“Generalizing results from trial to clinic is challenging, and future trials should aim to have more inclusive criteria,” the study concludes.