PMID- 34989781 OWN - NLM STAT- MEDLINE DCOM- 20220314 LR - 20230417 IS - 2374-2445 (Electronic) IS - 2374-2437 (Print) IS - 2374-2437 (Linking) VI - 8 IP - 2 DP - 2022 Feb 1 TI - Association of Radiation Therapy With Risk of Adverse Events in Patients Receiving Immunotherapy: A Pooled Analysis of Trials in the US Food and Drug Administration Database. PG - 232-240 LID - 10.1001/jamaoncol.2021.6439 [doi] AB - IMPORTANCE: Immune checkpoint inhibitors (ICIs) and radiation therapy (RT) are widely used to treat various cancers, but little data are available to guide clinicians on ICI use sequentially with RT. OBJECTIVE: To assess whether there is an increased risk of serious adverse events (AEs) associated with RT given within 90 days prior to an ICI. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were pooled from 68 prospective trials of ICIs submitted in initial or supplemental licensing applications in the US Food and Drug Administration (FDA) databases through December 2019. Two cohorts were generated: (1) patients who received RT within the 90 days prior to beginning ICI therapy and (2) those who did not receive RT within the 90 days prior to beginning ICI therapy, and AE frequencies were determined. A 1:1 propensity score-matched analysis was performed. INTERVENTIONS: All patients received an ICI (atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab, or pembrolizumab); 1733 received RT within the 90 days prior to starting ICI therapy, and 13 956 did not. MAIN OUTCOMES AND MEASURES: The primary outcome was frequency and severity of AEs. Incidence of AEs was compared descriptively between participants who did vs did not receive RT in the propensity score-matched set. Because all analyses are exploratory (ie, not preplanned and no alpha allocated), assessment for statistical significance of the differences between groups was not considered appropriate. RESULTS: A total of 25 469 patients were identified; 8634 were excluded because they lacked comparators who had received RT (n = 976), did not receive an ICI (n = 4949), received RT outside of the target window (n = 2338), or had missing data in 1 or more variables used in the propensity analysis (n = 371), leaving 16 835 patients included in the analysis. The majority were younger than 65 years (9447 [56.1%]), male (10 459 [62.1%]), and White (13 422 [79.7%]). Patients receiving RT had generally similar rates of AEs overall to those patients who did not receive RT. The average absolute difference in rates across the AEs was 1.2%, and the difference ranged from 0% for neurologic AEs to 8% for fatigue. No difference in grade 3 to 4 AEs was observed between the 2 groups (absolute difference ranged from 0.01% to 2%). These findings persisted after propensity score matching. CONCLUSIONS AND RELEVANCE: In this pooled analysis, administration of an ICI within 90 days following RT did not appear to be associated with an increased risk of serious AEs. Thus, it would appear to be safe to administer an ICI within 90 days of receiving RT. These findings should be confirmed in future prospective trials. FAU - Anscher, Mitchell S AU - Anscher MS AD - US Food and Drug Administration, Silver Spring, Maryland. FAU - Arora, Shaily AU - Arora S AD - US Food and Drug Administration, Silver Spring, Maryland. FAU - Weinstock, Chana AU - Weinstock C AD - US Food and Drug Administration, Silver Spring, Maryland. FAU - Amatya, Anup AU - Amatya A AD - US Food and Drug Administration, Silver Spring, Maryland. FAU - Bandaru, Pradeep AU - Bandaru P AD - Palantir Technologies, Inc, Washington, DC. FAU - Tang, Chad AU - Tang C AD - University of Texas MD Anderson Cancer Center, Houston. FAU - Girvin, Andrew T AU - Girvin AT AD - Palantir Technologies, Inc, Washington, DC. FAU - Fiero, Mallorie H AU - Fiero MH AD - US Food and Drug Administration, Silver Spring, Maryland. FAU - Tang, Shenghui AU - Tang S AD - US Food and Drug Administration, Silver Spring, Maryland. FAU - Lubitz, Rachael AU - Lubitz R AD - Palantir Technologies, Inc, Washington, DC. FAU - Amiri-Kordestani, Laleh AU - Amiri-Kordestani L AD - US Food and Drug Administration, Silver Spring, Maryland. FAU - Theoret, Marc R AU - Theoret MR AD - US Food and Drug Administration, Silver Spring, Maryland. FAU - Pazdur, Richard AU - Pazdur R AD - US Food and Drug Administration, Silver Spring, Maryland. FAU - Beaver, Julia A AU - Beaver JA AD - US Food and Drug Administration, Silver Spring, Maryland. LA - eng GR - P30 CA016672/CA/NCI NIH HHS/United States PT - Journal Article PT - Meta-Analysis PL - United States TA - JAMA Oncol JT - JAMA oncology JID - 101652861 RN - 0 (Ipilimumab) RN - 31YO63LBSN (Nivolumab) SB - IM CIN - JAMA Oncol. 2022 Feb 1;8(2):240-241. PMID: 34989784 EIN - JAMA Oncol. 2022 Feb 1;8(2):306. PMID: 35175305 CIN - Strahlenther Onkol. 2022 May;198(5):503-505. PMID: 35357512 CIN - JAMA Oncol. 2022 Jul 1;8(7):1073. PMID: 35511133 CIN - JAMA Oncol. 2022 Jul 1;8(7):1072. PMID: 35511138 CIN - Strahlenther Onkol. 2022 Nov;198(11):1049-1051. PMID: 36053306 MH - Humans MH - *Immunotherapy/adverse effects MH - Ipilimumab/adverse effects MH - Male MH - *Neoplasms/drug therapy/radiotherapy MH - Nivolumab/adverse effects MH - United States/epidemiology MH - United States Food and Drug Administration PMC - PMC8739815 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2022/01/07 06:00 MHDA- 2022/03/15 06:00 PMCR- 2023/01/06 CRDT- 2022/01/06 12:25 PHST- 2022/01/07 06:00 [pubmed] PHST- 2022/03/15 06:00 [medline] PHST- 2022/01/06 12:25 [entrez] PHST- 2023/01/06 00:00 [pmc-release] AID - 2787952 [pii] AID - coi210091 [pii] AID - 10.1001/jamaoncol.2021.6439 [doi] PST - ppublish SO - JAMA Oncol. 2022 Feb 1;8(2):232-240. doi: 10.1001/jamaoncol.2021.6439.