NEW YORK (Reuters Health) – Treatment with an immune-checkpoint inhibitor (ICI) within three months following radiation therapy (RT) does not appear to increase the risk of serious adverse events, according to a pooled analysis of patient-level data from prospective trials in the U.S. Food and Drug Administration (FDA) database.
This review of the compendium of FDA data “provides additional assurances that sequential RT and ICIs is tolerable and safe. It suggests that when RT leads immunotherapy, the dance goes reasonably smoothly,” write the authors of an editorial published with the study in JAMA Oncology.
ICIs and RT are widely used to treat numerous cancers, allied window treatments but data to guide clinicians on ICI use sequentially with RT are lacking.
To better gauge the adverse effects associated with ICI-RT combinations within a certain time frame, Dr. Mitchell Anscher at the FDA and colleagues analyzed data from 68 relevant clinical trials involving 16,835 cancer patients who received RT within 90 days prior to ICI treatment. Most were younger than age 65 (56%), male (62%) and white (80%).
All patients received an ICI (atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab, or pembrolizumab); 1,733 received RT within the 90 days before starting ICI therapy, and 13,956 did not.
Patients receiving RT had generally similar rates of adverse events overall to those who did not receive RT.
The average absolute difference in rates across the adverse events was 1.2%, and the difference ranged from 0% for neurologic AEs to 8% for fatigue. There was no difference in grade-3 to -4 AEs between the two groups (the absolute difference ranged from 0.01% to 2%). These findings persisted after propensity-score matching.
This was a “quite expansive” analysis, spanning studies from 2003 through 2019 with propensity-score analysis used to compare patients who received RT with those who did not, note editorialists Dr. Fiyinfolu Balogun of Memorial Sloan Kettering Cancer Center in New York and Dr. David Raben of the University of Colorado, in Aurora.
The data suggest a “modest increase in fatigue, thrombocytopenia, and pneumonitis with the addition of RT; however, this was only apparent in grade 1 to 2 adverse events,” they point out.
Of note, due to insufficient numbers, a subgroup analysis of anti-programmed cell death 1 (anti-PD-1) versus anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) was not performed – “a relevant point owing to the well-established difference in toxicity based on ICI subtype,” Drs. Balogun and Raben say.
A notable limitation of the analysis acknowledged by the authors is the absence of key RT details such as dose per fraction, treatment site and volumes irradiated.
“This can be critical information that affects both acute and long-term toxic effects, as well as potentially contributing to chronic immunosuppression depending on the volumes that include uninvolved lymph node basins,” Dr. Balogun and Dr. Raben say.
Understanding the toxicity from combined ICI and RT is increasingly important given the expansion of immunotherapy to the adjuvant/neoadjuvant setting, they add.
“In addition, we are increasingly combining ICIs, concurrent chemotherapy, and precision medicine with RT to further improve outcomes. Patients exposed to this combined therapy in the adjuvant setting are more likely to have longer survival whereby the effect of toxic effects on quality of life becomes more pronounced,” they write.
The analysis had no specific funding and the authors disclosed no relevant conflicts of interest.
SOURCE: https://bit.ly/34zSaIh and https://bit.ly/3Fi37e8 JAMA Oncology, online January 6, 2022.
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