ROME — Global data are quite reassuring that the risk of cancer in children taking etanercept is elevated very little if at all, judging from data from two studies.
In all, 18 malignancies in etanercept-treated pediatric and young adult patients were reported worldwide in clinical trials, registries, postmarketing surveillance studies, and published case reports during the 11-year period of 1998-2009. The youths were placed on the tumor necrosis factor inhibitor mainly for juvenile idiopathic arthritis (JIA) or psoriasis.
This translates to a cancer incidence rate of 1.5 cases per 10,000 patient-years of exposure to etanercept (Enbrel). That's essentially the same as the projected background rate of 1.47 cases per 10,000 patient-years in normal 4- to 17-year-olds in the National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) database, Dr. Peter McCroskery reported.
Moreover, the figure of 1.5 cancers per 10,000 patient-years probably overestimates the true incidence of malignancies in etanercept-treated youths. For one thing, 4 of the 18 cases could not be confirmed. And three of four leukemias included in the series were diagnosed less than 4 months after initiation of etanercept, in one case after only 29 days on the biologic; the timing of these three cases suggests they may very well have involved early musculoskeletal symptoms of leukemia being initially mistaken for juvenile idiopathic arthritis, noted Dr. McCroskery of Amgen Inc.
Of the 18 patients, 15 were also receiving immunosuppressive agents linked to cancer. These included cyclophosphamide, methotrexate, cyclosporine, and azathioprine. Three patients had also received other biologic agents.
These caveats, confounding because of concomitant immunosuppressive medications and the rarity of pediatric cancers, underscore the difficulty in attempting to assess the true risk of cancer associated with the use of etanercept in children and adolescents, the physician said.
“Concerns have been raised recently about a potential link between the use of TNF inhibitors and the development of malignancies in adults and children. This study was an attempt to be completely and totally transparent and let the data speak for themselves,” he said in an interview.
The Amgen-sponsored study yielded no signal of an increased risk of cancer overall in association with etanercept. There was a slight signal for lymphoma, with an incidence of 1 case per 10,000 person-years of treatment in 4- to 17-year-olds, compared with a background rate of 0.26 per 10,000 person-years based upon SEER data.
However, as Dr. McCroskery noted, another study presented at the European congress concluded that the risk of cancer is already increased in JIA patients who've never been on a biologic therapy.
Dr. Melanie J. Harrison presented a retrospective cohort study involving 3,605 biologics-naive JIA patients and 37,689 matched controls without JIA. The data were extracted from a claims database including more than 60 million commercially insured Americans. The risk of cancer in the biologics-naive JIA group was elevated 2.8-fold.
“These findings suggest that the underlying risk of cancer in JIA is elevated, and any risk associated with the use of biologics should be interpreted in this context,” according to Dr. Harrison of Pfizer Inc.
Disclosures: Dr. McCroskery is an employee of Amgen, which makes Enbrel. Dr. Harrison's employer, Pfizer, is a partner of Amgen.