medwireNews: Treatment with immune checkpoint inhibitors (ICIs) within 90 days of radiotherapy (RT) does not lead to a “meaningful increase” in rates of serious adverse events (AEs), say researchers who conducted a pooled analysis of US FDA registry data.
“Patients who had received RT had slightly numerically higher rates of fatigue, endocrinopathies, and pneumonitis” than those who had not, but “[t]hese differences were due to low-grade (grade 1-2) AEs,” they report in JAMA Oncology.
The study included data on 16,835 participants of 68 trials of ICIs submitted to the FDA as part of the initial or supplemental licensing applications between February 2003 and December 2019. The most common tumor type in the cohort was lung cancer, followed by melanoma, bladder cancer, and kidney cancer.
The majority (83%) of patients had not received RT prior to initiating ICI treatment, 11% had received RT within 90 days of starting ICIs, and 6% had received RT more than 90 days before initiating ICIs.
In the overall cohort, the incidence of fatigue, endocrinopathies, and pneumonitis was numerically higher among patients who received RT within 90 days of starting ICI therapy versus those who did not receive RT, and the incidence of pneumonitis was similarly numerically higher among those who received RT more than 90 days before starting ICI therapy.
Chana Weinstock (US Food and Drug Administration, Silver Spring, Maryland, USA) and colleagues highlight that the differences appeared to be driven by higher rates of low-grade AEs, “as there was no difference in grade 3 to 4 AEs” between groups.
After propensity-score matching, patients in the RT within 90 days group continued to have numerically increased rates of all-grade fatigue (53.5 vs 51.1%), pneumonitis (6.8 vs 4.6%), and also thrombocytopenia (3.4 vs 2.1%), but not endocrinopathies, compared with those in the no-RT group.
There was, however, no increase in the incidence of all-grade pneumonitis among patients who received RT more than 90 days before ICI treatment versus those who did not receive RT.
Discussing the limitations of the analysis, the researchers say: “Despite the prospective nature of the studies in the FDA database, there were considerable amounts of missing data pertaining to important factors, such as numbers of prior lines of therapy, which may affect the risk of AEs from either therapy.”
They note, however, that the sample size was large enough “to permit an exploratory analysis using propensity score matching in more than 5000 patients,” which “provides some reassurance that an important safety signal was not missed.”
Nevertheless, they add that “this preliminary suggestion that combinations of RT and ICIs may be safe to use will require prospective confirmation, and such trials are under way.”
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