Only 13% of Patients Eligible for Checkpoint Inhibitors Respond to Them

By Marilynn Larkin

May 14, 2019

NEW YORK (Reuters Health) - About 44% of cancer patients may be eligible for an FDA-approved checkpoint inhibitor drug, yet approximately 13% will respond to them, researchers say.

"We are a bit disappointed by the percentage and feel it is at odds with Superbowl ads and the juggernaut of hype regarding these drugs," Dr. Vinay Prasad of Oregon Health and Science University in Portland told Reuters Health by email. "They help many patients, but they don't help most patients. Most cancer patients would not benefit even if the drugs were free."

"I hope someday we can have an environment where we can speak honestly about cancer drugs so patients have realistic optimism and are not influenced by hype or misleading rhetoric," he added.

To calculate the percentage of patients who could potentially be candidates for, and thus benefit from, checkpoint inhibitors approved from 2011 to 2018, Dr. Prasad and Dr. Alyson Haslam, also of Oregon Health and Science University, used annual cancer death numbers from the American Cancer Society as a stand-in for annual incidence of advanced or metastatic disease.

These incidences were considered the pool of potential candidates and adjusted according to the drugs' labels and qualifiers to determine the percentage of patients eligible to receive them.

The researchers also looked at measures of response (complete plus partial) according to the FDA label, and published reports estimating overall response rates using various trial designs.

As reported online May 3 in JAMA Network Open, six checkpoint inhibitors were approved for 14 indications between March 25, 2011 and August 17, 2018. The estimated percentage of cancer patients who were eligible for those drugs increased from 1.54% in 2011 to 43.63% in 2018.

By contrast, the percentage of cancer patients estimated to respond to checkpoint inhibitors was 0.14% in 2011 when ipilimumab was approved for unresectable or metastatic melanoma. This increased to 5.86% by 2015, and to 12.46% by 2018.

Dr. Daniel Catenacci, Director, Interdisciplinary Gastrointestinal Oncology Program and Assistant Director, Translational Research, Comprehensive Cancer Center at UChicagoMedicine, who coauthored a related editorial, told Reuters Health, "This study quantitates the disturbing trend that, despite the expansion in the number of patients eligible for expensive and potentially toxic immune checkpoint inhibitors, the ratio of those benefitting is decreasing."

"Concerningly," the editorial points out, "the ratio of the percentage benefit from (checkpoint inhibitors) to the percentage of cancers affected by (checkpoint inhibitors) over time peaked in 2014 but then dropped as more approvals ensued, indicating that the percentage of individuals who are eligible for (checkpoint inhibitors) through FDA approvals has grown at a higher rate than the percentage of individuals who may actually benefit from them."

"This was not all that surprising to me," Dr. Catenacci said in an email. "The hype of these agents has led to unrealistic expectations and lenient conditional approvals. Follow-up confirmatory studies have been negative in a number of instances."

"With better patient selection and earlier disease indications, there is no doubt that eligibility and benefit estimates will change over time," added Dr. Catenacci, who is also Associate Editor of the journal. "Patients should be encouraged to enroll on clinical studies attempting to answer the important questions such as who should be getting immune checkpoint inhibitor therapy alone, in combination (and with what), or not at all."


JAMA Netw Open 2019.