Study Examines Immunotherapy Outcomes in Patients With Solid Tumors Who Are Ineligible for Clinical Trials

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Patients with solid tumors who are ineligible for clinical trials receive immune checkpoint inhibitors at greater rates than patients who are eligible, despite no survival benefit, according to a recent study by researchers at the Perelman School of Medicine at the University of Pennsylvania. The study, published by Parikh et al in JAMA Oncology, suggests that the positive results for phase III clinical trial participants receiving immune checkpoint inhibitor treatment may not translate to patients who are ineligible for clinical trials because of factors such as organ dysfunction.

Immune checkpoint inhibitors are part of the standard of care for patients with many advanced solid tumors and are generally associated with improved survival. Randomized phase III immune checkpoint inhibitor clinical trials have traditionally excluded patients with advanced cancer because of poor performance status or disease-related organ dysfunction, which may increase the risk for adverse events associated with immune checkpoint inhibitor treatment. Because of the absence of randomized trial data that define the impact of immune checkpoint inhibitor treatment on patients with solid tumors who are deemed ineligible for trials, researchers conducted a retrospective study to look at treatment rates and outcomes for these patients, as compared with those patients for whom trial data are available.

Study Details

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 whether the frequency of use and effectiveness of immune checkpoint inhibitors in this patient population with more advanced disease are similar to those with less advanced disease, as was studied in the clinical trials. They found that use of immune checkpoint inhibitor monotherapy increased over the study period, between 2014 to 2019, up to 30.2% among patients who would be trial-ineligible, compared with 19.4% 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, 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 immune checkpoint inhibitor monotherapy or combination therapy compared with other treatment options. The study suggests the cautious use of immune checkpoint inhibitor combination therapy for trial-ineligible patients because of 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 immune checkpoint inhibitors and to be honest with the limitations of current supporting research to date,” said Ronac Mamtani, MD, MSCE, Assistant Professor of Hematology-Oncology at the Abramson Cancer Center at Penn. “Even though immune checkpoint inhibitors have a better side-effect profile for most patients, positive results in phase III trials may not necessarily translate to improved quality of life and survival for all patients.”

Dr. Parikh, of Perelman School of Medicine at the University of Pennsylvania, is the corresponding author of the JAMA Oncology article.

Disclosure: This study was funded by a Conquer Cancer Foundation Young Investigator Award, the National Cancer Institute, and the Catholic Medical Center Research Foundation. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.