Checkpoint inhibitors got to melanoma, non–small cell lung cancer, and renal cell carcinoma patients quickly in clinical practice after Food and Drug Administration approval – usually within 4 months – but the patients treated in clinical settings tended to be older than those treated in trials, which has caused concern about whether real-world efficacy will prove to be the same, according to a study in.
“Such rapid adoption stands in contrast to older estimates that suggest it takes years or even decades for new treatments to be adopted,” wrote lead author, professor of medicine at Yale University, New Haven, and his coauthors. “We found significant differences in age between patients treated in practice and those treated in trials, which highlights the need to clarify the risks and benefits of checkpoint inhibitors in general populations of patients.”
Researchers drew data on nivolumab and pembrolizumab use from the Flatiron Health longitudinal EHR database, which included 233 academic and community oncology practices. In each of the three disease cohorts, adoption was seen within 4 months for at least 60% of patients. Uptake was quickest for the melanoma patients, 76% of whom received a checkpoint inhibitor within 4 months, investigators wrote. Factors for the fast adoption could include high disease severity, a preference for novelty, perceived gains over existing treatments, and promotional activities, such as media reports and advertising directly to consumers, they wrote.
More patients in real-world practice were aged 65 years or older, ranging from as little as 61% at the lowest end of the range at one center to as much as 64% at the highest end at another. In the clinical trials, the percentage of patients aged 65 years or older ranged from 32% in one trial to 41% in another. Researchers wrote that these higher real-world rates are concerning because there are still questions regarding whether differences in immune responses will cause differences in efficacy between older and younger patients, as well as safety considerations among different age groups.
“Although data suggest that outcomes are similar between older and younger patients receiving anti–PD-1 agents for melanoma, there is little evidence to guide anti–PD-1 treatment of older patients with NSCLC [non–small cell lung cancer],” Dr. Gross and his coinvestigators wrote.
Investigators wrote that the findings are cause for caution.
“As FDA officials develop more flexible standards for approval, which the 21st Century Cures Act requires them to do, it is possible that many patients will receive drugs before much is known about clinical outcomes,” Dr. Gross said. “Further integrations of real-world evidence might allow the FDA to better assess the drugs that they approve on the basis of nonrepresentative trial participants.”
SOURCE: Gross C et al. JAMA Oncol. 2018 May 10..