In a recent article in the Journal of Clinical Oncology, researchers conducted a systematic review and meta-analysis to establish the prevalence of IRRs in patients with genitourinary cancers (GC) who were treated with immune checkpoint inhibitors (ICIs).

The authors wrote, “Immune checkpoint inhibitors are widely used to treat genitourinary cancers, particularly urothelial carcinoma (UC) and renal cell carcinoma (RCC). Infusion-related reactions (IRRs) have been reported in up to 20% of all patients treated with ICIs.”

The authors also noted that the risk of IRR differs with the type of ICI used, and the exact incidence of IRRs in patients with genitourinary cancers (GCs) remains uncertain.

The scientists conducted a systematic search utilizing literature from PubMed/MEDLINE, Embase, and Web of Science. They sought to find and examine data from phase III randomized clinical trials (RCTs) involving patients diagnosed with UC and RCC that assessed the use of ICIs (cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], programmed cell death protein 1 [PD-1], and programmed death-ligand 1 [PD-L1] inhibitors).

The odds ratio [OR] of grade 1 to 5 and grade 3 to 5 IRRs were computed and grouped by the random-effect model meta-analysis.

The authors noted that the meta-analysis was conducted and established on the following study types: “1) studies with a design [ICI plus treatment A (including placebo/observation) vs. treatment A]; 2) studies evaluating ICI monotherapy vs. chemotherapy in patients with UC; and 3) studies assessing ICI plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) vs. sunitinib in patients with RCC.”

When IRRs were documented in studies assessing oral VEGF-TKIs, IRRs were described as hypersensitivity or anaphylactic reactions, outlined in each RCT.

The researchers identified 12 RCTs involving 10,001 participants for the meta-analysis. One RCT assessed a CTLA-4 inhibitor, while the other RCTs assessed PD-1 or PD-L1 inhibitors.

The results revealed that the addition of ICIs to other systemic therapies was linked with “significantly greater rates of grade 1-5 IRRs (OR = 2.90, 95% confidence interval [CI]: 1.16-7.29, P = 0.02) but not of grade 3-5 IRRs (OR = 2.98, 95% CI: 0.64-13.74, P = 0.16).”

The results also revealed that in patients with UC, compared with chemotherapy, PD-1 or PD-L1 inhibitor monotherapy was not correlated with an upsurge in either grade 1-5 IRRs (OR = 0.86; 95% CI, 0.25-2.95; P = .81) or grade 3-5 IRRs (OR = 1.13; 95% CI: 0.07-18.19; P = .93).

The use of an ICI plus VEGF-TKIs in combination was not correlated with an increase in either grade 1-5 (OR = 5.43; 95% CI, 0.62-46.07; P = .13) or grade 3-5 IRRs (OR = 3.49; 95% CI: 0.64-19.04, P = .15) when compared with the receptor tyrosinase inhibitor, sunitinib, in patients with RCC. A sensitivity analysis that was conducted by eliminating studies evaluating the monoclonal antibody, nivolumab, did not change the overall results.

Based on their findings, the authors concluded that compared with the previous standard of care without ICIs, therapies with ICIs were not correlated with an augmented incidence of IRRs in GCs. The authors also noted that the addition of ICIs to other systemic therapies was, however, correlated with a heightened incidence of IRRs.

The authors wrote, “The latter merits further prospective evaluation and careful consideration while designing clinical trials.”

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