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PHILADELPHIA — Cancer patients who are ineligible for clinical trials receive immune checkpoint inhibitors (ICI) at greater rates than patients who are trial eligible despite no survival benefit, according to a new study by researchers at the Perelman School of Medicine at the University of Pennsylvania. The study, published in JAMA Oncology, suggests that the positive results for phase 3 clinical trial participants receiving ICI treatment may not translate to patients who are ineligible for trials due to factors such as organ dysfunction.

ICIs, a type of immunotherapy, are part of the standard of care for patients with many advanced solid tumors and are generally associated with improved survival. Randomized phase 3 ICI clinical trials have traditionally excluded advanced cancer patients because of poor performance status—an estimate of a patient’s ability to complete daily activities — or disease-related organ dysfunction, which may increase risk for adverse events associated with ICI treatment. Because of the absence of randomized trial data that defines the impact of ICI treatment on advanced cancer patients deemed ineligible for trials, researchers conducted a retrospective study to look at treatment rates and outcomes for these patients, as compared to those patients for whom trial data are available.

The nationwide study of 34,000 patients diagnosed with advanced solid tumors included those with metastatic or recurrent non-small cell lung cancer, urothelial cell cancer, renal cell cancer, and hepatocellular carcinoma. The researchers set out to determine if the frequency of use and effectiveness of ICIs in this patient population with more advanced disease is similar to those with less advanced disease, as was studied in the clinical trials. They found that use of ICI monotherapy increased over the study period, between 2014 to 2019, up to 30.2 percent among patients who would be trial-ineligible, compared to 19.4 percent among patients who would be trial-eligible.

“Patients with advanced cancers are in desperate need of treatment options, and immunotherapy provides a targeted approach worth studying further, especially in trial-ineligible patients,” said Ravi B. Parikh, MD, an assistant professor of Medical Ethics & Health Policy and Medicine at Penn. “Despite the lack of evidence and benefits for this vulnerable population, we found that oncologists used immunotherapy at faster rates for trial-ineligible patients. However, health care providers of patients with poor functional status or organ dysfunction should not assume immunotherapies will confer the same benefit as the populations studied in trials.”

The researchers did not find evidence of survival benefit among trial-ineligible patients receiving ICI monotherapy or combination therapy compared to other treatment options, and the study suggests the cautious use of ICI combination therapy for trial-ineligible patients due to the potential for early harm.

“While it makes sense to consider novel therapies like immunotherapies for trial-ineligible patients, it is essential to be alert when using ICI, and to be honest with the limitations of current supporting research to date,” said Ronac Mamtani, MD, MSCE, an assistant professor of Hematology-Oncology at the Abramson Cancer Center at Penn. “Even though ICIs have a better side-effect profile for most patients, positive results in phase 3 trials may not necessarily translate to improved quality of life and survival for all patients.”

This study was funded by a Conquer Cancer Foundation Young Investigator Award, the National Cancer Institute (K08 CA263541, P30 CA016520) and the Catholic Medical Center Research Foundation.

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Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $8.9 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $496 million awarded in the 2020 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center—which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report—Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is powered by a talented and dedicated workforce of more than 44,000 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2020, Penn Medicine provided more than $563 million to benefit our community.

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