In a pooled analysis of individual patient data from trials in the U.S. Food and Drug Administration database reported in JAMA Oncology, Anscher et al found that patients with cancer receiving radiotherapy within 90 days prior to the start of immune checkpoint inhibitor treatment were not at increased risk for severe adverse events vs those not receiving radiotherapy.
As stated by the investigators, “Immune checkpoint inhibitors and radiation therapy are widely used to treat various cancers, but little data are available to guide clinicians on immune checkpoint inhibitor use sequentially with radiation therapy.”
Study Details
The analysis included a total of 16,835 eligible patients who received an immune checkpoint inhibitor (atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab, or pembrolizumab), including 1,733 who received radiotherapy within 90 days prior to starting immune checkpoint inhibitor therapy, 13,956 who did not receive radiotherapy, and 1,146 who received radiotherapy ≥ 90 days before starting immune checkpoint inhibitor treatment.
The data presented are from the comparison of the radiotherapy ≤ 90 days vs no radiotherapy groups in the total population and in a propensity score–matched analysis including 1,662 patients in each of these two groups with matching for performance status, number of prior lines of therapy, cancer type, type of immune checkpoint inhibitor–based therapy, age, sex, race/ethnicity, and country. Adverse event categories analyzed were neutropenia, thrombocytopenia, pneumonitis, colitis, hepatitis, myocarditis, neurologic, skin, kidney, endocrine, fatigue, diarrhea, and musculoskeletal.
In this pooled analysis, administration of an immune checkpoint inhibitor within 90 days following radiotherapy did not appear to be associated with an increased risk of serious adverse events. Thus, it would appear to be safe to administer an immune checkpoint inhibitor within 90 days of receiving radiotherapy.— Anscher et al
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Key Findings
The radiotherapy ≤ 90-day group had similar rates of adverse events vs the no-radiotherapy group. The average absolute difference in rates across any-grade adverse events was 1.2%, with differences ranging from 0% for neurologic adverse events to 7.6% for fatigue.
No difference in grade 3 or 4 adverse events was observed between groups, with absolute differences ranging from < .1% (myocarditis) to 0.8% (pneumonitis). The radiotherapy ≤ 90-day group had slightly higher rates of any-grade fatigue (53.1% vs 45.5%, grade 3–4 in 4.8% in both), endocrinopathies (14.8% vs 13.4%, grade 3–4 in 1% in both), and pneumonitis (6.8% vs 3.8%, grade 3–4 in 1.9% vs 1.1%). The most common grade 3 or 4 adverse events were fatigue and diarrhea (3.9% vs 4.3%).
Overall findings were similar in the propensity score–matched analysis. The radiotherapy ≤ 90-day group had slightly higher rates of any-grade pneumonitis (6.8% vs 4.6%), thrombocytopenia (3.4% vs 2.1%), fatigue (53.5% vs 51.1%), and kidney adverse events (0.4% vs 0.2%), whereas rates were similar for endocrinopathies (15.0% vs 14.8%) and slightly lower for skin adverse events (0.1% vs 0.3%).
The investigators concluded, “In this pooled analysis, administration of an immune checkpoint inhibitor within 90 days following radiotherapy did not appear to be associated with an increased risk of serious adverse events. Thus, it would appear to be safe to administer an immune checkpoint inhibitor within 90 days of receiving radiotherapy. These findings should be confirmed in future prospective trials.”
Chana Weinstock, MD, of the U.S. Food and Drug Administration, is the corresponding author for the JAMA Oncology article.
