Adverse events associated with immune checkpoint inhibitors may be more common than reported in trials that led to FDA approvals of those agents, according to a study presented at Palliative and Supportive Care in Oncology Symposium.
“There certainly wasn’t anything wrong with the original trials. Any time you have a new medication, there is always a learning curve in terms of what’s to be expected,” Elizabeth Jane Cathcart-Rake, MD, professor of medicine at Mayo Clinic in Rochester, Minnesota, told HemOnc Today. “Over time, we start learning more by talking to patients and actually understanding what to look for. Hopefully, over the next several months, we will get more information as far as how these side effects are related to, say, a tumor type or demographics.”
Researchers reviewed claims data from the U.S. commercial insurance database OptumLabs Data Warehouse to identify patients with non-small cell lung cancer who received the PD-1 or PD-L1 immune checkpoint inhibitors nivolumab (Opdivo, Bristol-Myers Squibb), pembrolizumab (Keytruda, Merck) or atezolizumab (Tecentriq, Genentech) between 2015 and 2017.
Researchers then looked at the frequency of immune-related adverse events.
The analysis included 2,798 patients with NSCLC (median age at immunotherapy initiation, 69 years; interquartile range, 60-75; 55.6% male).
In this group, 1,998 received nivolumab, 699 received pembrolizumab and 101 received atezolizumab.
Most patients (n = 1,463) received these agents as second-line therapy, and the majority of this group (50.8%; n = 744) received alkylating agents and antimetabolites prior to immunotherapy.
An analysis of immune-related adverse events showed 9.2% of patients experienced hypothyroidism, 5.7% experienced anemia, and 2.8% experienced acute kidney injury. Gastrointestinal and cardiac events were relatively rare.
Only about 14% of trials report adverse events at the time of publication, Cathcart-Rake and colleagues said.
However, the KEYNOTE-024 trial, which compared pembrolizumab with chemotherapy, allowed the researchers to compare initial results with population-based data.
KEYNOTE-024 reported 0.6% of patients had hypophysitis, a rare condition that involves acute or chronic inflammation of the pituitary gland. Cathcart-Rake’s analysis, however, found that 2.4% of patients in that trial experienced hypophysitis.
One potential limitation of the study was that researchers could not account for people who did not have insurance. Analyses of data are ongoing.
Despite the findings, Cathcart-Rake told HemOnc Today that she would still recommend treatment with immune checkpoint inhibitors.
“It’s still a great therapy. I think the biggest takeaway is that population data can complement the trial data,” Cathcart-Rake said. “I think we are getting complementary information that enriches our understanding of these side effects.”– by John DeRosier