Immunotherapy toxicity in the curative setting.

e14579 Background: Immune checkpoint inhibitors (ICI) improve survival in the curative setting. Understanding the impact, severity, and long-term toxicity is critical given the implication for survivorship and use of healthcare resources. Study objectives were to quantify the incidence and severity of acute and long-term adverse events (AE) and immune-related AE (irAE) in this setting. Secondary objectives include assessment for associations between trial factors with the incidence/severity of AE and to assess AE reporting across studies. Methods: A retrospective review of all FDA-approved solid-tumor, curative treatment regimens including ICI was performed. Included studies were clinical trials, follow-up studies, or post-marketing AE reports. Studies were excluded if they lacked AE data. Data Sources included the FDA drug database and systematic searches in PubMed, Cochrane Library, and Embase using keywords “immunotherapy,” “curative setting,” and “toxicity.” Data was extracted on study type, regimen, population, outcomes, acute and long-term AE. AE were graded using CTCAE. Organ/system-specific classifications were prioritized, and attention was paid to reporting of irAE. SPSS version 22 was used to calculate descriptive statistics and odds ratio. Follow-up duration was evaluated by determining mean and median lengths reported across studies. Results: Overall, 23 manuscripts were identified (14 original trials; 9 follow-up studies), with 5 trials and 3 follow-up studies examining ICIs in combination with other treatments. Common AE included fatigue, nausea, diarrhea, and pruritis. The rates of any-grade AE increased from 80.1% in original studies to 88.3% in follow-up studies; grade 3-5 AE increased from 34.1% to 53.3%. Among studies with both baseline and follow-up data (n = 9), the average difference in AE rates was 8.2%. Only 7 studies specified if the toxicity was considered an irAE, reporting only on hypo/hyperthyroid, colitis, hypophysitis (n = 5 studies), and pneumonitis (n = 3 studies). Hepatitis, pancreatitis, and myositis were only reported on as separate irAE once. Colitis was the most common irAE in follow-up studies (7.2%). The average incidence of immune-related AE for single-agent ICI was 65.3% versus combination therapy 82.7%. In the primary papers, immunotherapy was associated with a higher risk of any grade AE (OR = 2.12) and grade 3-5 AE (OR = 2.16) compared with control groups. Follow-up studies demonstrated continued risk of grade 3-5 AE (OR = 2.77), particularly in nausea, fatigue, and diarrhea. Conclusions: There is a significant burden of AE associated with curative-intent ICI therapy, with increased incidence and severity over time; however, there is limited data on frequency and impact of irAE. Clinicians and trialists should be vigilant in documenting specifically if an irAE has occurred and its respective grade in order to improve understanding of the burden of these issues on the healthcare system.

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