Lung cancer

The sobering reality of checkpoint inhibitors: only 13% of cancer patients are responders

High public expectations for checkpoint inhibitor therapy need to be tempered by the reality of low absolute numbers of cancer patients who benefit from them, US researchers say.

While almost half of cancer patients (46.3%) are now potentially eligible for immune checkpoint inhibitor treatment, only 12.46% of patients are likely to be responders, according to new estimates based on US oncology indications.

The findings, published in JAMA Network Open, also show that while checkpoint inhibitors may have dramatic impact in rare cancers, most of the absolute benefit is being seen in a few common cancers such as non-small cell lung cancer (NSCLC).

Researchers estimated the number of cancer patients who would be eligible for treatment with the six checkpoint inhibitors approved in the US for oncology indications since 2011. They derived their estimates of patient numbers based on FDA indication criteria such as tumour type and PD-L1 level.

They found that the number of patients eligible for ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab and durvalumab increased from 1.54% in 2011 to 46.3% by 2018.

The absolute number of cancer patients responding to immunotherapy, extrapolated from response rates in FDA trial databases, increased from 0.14% in 2011 to 12.46% in 2018.

The greatest absolute benefit was seen in patients with NSLC, who accounted for 7% of cancer responses to immunotherapy, including patients with PD-L1 between 0% and 50% who typically have poor relatively responses compared to those with PD-L1 over 50%.

The study authors said there had been well-justified excitement and rapid uptake for checkpoint inhibitors because of their ability to generate durable responses in many hitherto intractable malignant tumours.

However the modest responses seen in terms of absolute numbers should encourage oncologists, journalists and policymakers have more open and honest discussions about checkpoint inhibitors, they suggested.

“The observations in this article are sobering and remind us to keep expectations of immune checkpoint inhibitors realistic,” said an accompanying commentary by Dr Daniel Catenacci, an oncologist at the University of Chicago.

“As the dust settles and the wave of hysteria ebbs, studies like this lend support to physicians as they attempt to explain to most of their patients with cancer the reason they are not receiving immune checkpoint inhibitors – because these drugs are not appropriate for them.”

Dr Catenacci  noted the study also showed that while the number of patients eligible for expensive and potentially toxic checkpoint inhibitors is expanding, the ratio of those benefitting is decreasing.

“As responsible and informed oncologists, it is vital that we use [checkpoint inhibitors] judiciously with an eye to maximising benefit, as difficult as this may be while patients demand [checkpoint inhibitors] based on the press, the current buzz, and patient-directed advertising,” he wrote.

The benefit-to-eligibility ratio may be improved by maximising the use of biomarkers, he suggested.

“For example, biomarkers such as PD-L1 immunohistochemistry, with good negative predictive value, are imperative because patients with PD-L1–negative cancers derive minimal benefit with monotherapy [checkpoint inhibitors], thereby limiting eligibility via this selection,” he wrote.

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