Percentage of cancer patients eligible for therapy with immune-checkpoint inhibitors dropping

Last Updated: 2020-03-19

By Will Boggs MD

NEW YORK (Reuters Health) - The percentage of U.S. patients with cancer who are eligible for immune-checkpoint inhibitor (ICI) drugs is lower than previous estimates, researchers report.

"Even with the expanded eligibility to checkpoint-inhibitor drugs because of the approval of these drugs for triple-negative breast cancer, the total estimated eligibility was lower than our previous estimates," said Dr. Alyson Haslam from Oklahoma State University, in Tulsa.

"Our previous estimates indicated increasing eligibility over time, but taking into account the results of confirmatory studies, increasing eligibility in light of more drug approvals for more indications may not always be true, especially when the results of post-marketing studies become available," she told Reuters Health by email.

In 2019, based on 2018 data, Dr. Haslam and colleagues estimated that 43.6% of U.S. patients with cancer were eligible for ICI therapy and that up to 12.5% of patients respond to it. Since then, the U.S. Food and Drug Administration (FDA) has revised some ICI drug labels, and postmarketing studies for several drugs have failed to show improvement in overall survival or progression-free survival.

In the current study, taking into account these factors, Dr. Haslam's team estimates that 36.1% or 38.5% of U.S. cancer patients are eligible for ICI drugs, depending on whether the FDA limits apply to all immunotherapies or only to pembrolizumab and atezolizumab, respectively.

The more conservative estimate translates into an upper bound of more than 233,000 patients with cancer, the researchers report in JAMA Network Open.

The estimated total responses to these drugs were 10.9% and 11.4%, respectively, for the two scenarios.

Up to 9.0% of people who were eligible for ICIs in 2018 were subsequently ineligible because of negative confirmatory trials. Increases in eligibility from other indications (most notably, triple-negative breast cancer) were more than offset by decreases in eligibility from hepatocellular, urothelial and gastric cancers.

"These results suggest that physicians should be cautious in their expectations for checkpoint-inhibitor drugs in oncology," Dr. Haslam said. "While we certainly do not want to withhold drugs from patients because of lengthy studies and approval processes, we also want to make sure that the drugs that are approved have actual benefit, in terms of the number of patients who are both eligible and have a response to them. Patients deserve this, especially considering the financial costs of these drugs."

Dr. Kristian Hargadon from Hampden-Sydney College, in Virginia, who recently reviewed FDA-approved ICIs, told Reuters Health by email, "That these benefits were not seen for some cancer types when data from larger phase III trials were analyzed is certainly disappointing, but it should be noted that ICI therapy still benefits a large percentage of patients with diverse cancer types, and the duration of responses in many of these patients is often significantly longer than that achieved with non-ICI-based therapies."

"Moreover, important lessons from unsuccessful phase III trials have led to refined indications for ICI therapy in some instances, targeting the use of this therapy more specifically to particular patient cohorts most likely to receive clinical benefit," he said.

"These findings highlight what is already an emerging trend in cancer medicine, which is the need to identify appropriate biomarkers indicative of patient response to therapy," said Dr. Hargadon, who was not involved in the study. "Restricting ICI therapy to the cohort of patients most likely to respond not only benefits those patients directly but also allows a more appropriate course of action to be taken for those patients who are likely not to respond to ICI regimens. Such ICI-ineligible patients can then receive an alternative and perhaps more appropriate course of action earlier during the course of their cancer's progression."

"Physicians should understand that ICI therapy is not a one-size-fits-all approach to cancer treatment," he added. "The success of cancer immunotherapy is indeed real, but many factors must be considered when determining 1) whether ICI therapy is appropriate and 2) whether combinatorial strategies might extend the reach of ICI therapy to broader patient populations."

SOURCE: https://bit.ly/2wS8hjw JAMA Network Open, online March 9, 2020.