Background: Gefapixant represents an emerging therapy for patients with RCC/UCC.

Objectives: We aimed to evaluate the efficacy and safety of gefapixant for treatment of adults with RCC/UCC.

Methods: We searched MEDLINE, EMBASE, CENTRAL, and the Web of Science from Nov 2014 to Dec 2022 for randomized controlled trials (RCTs). We included both parallel and crossover RCTs that compared, in patients with RCC/UCC, either gefapixant with placebo, or two or more doses of gefapixant with or without placebo. Pairs of independent reviewers screened abstracts and full texts of potentially eligible articles. After duplicate data extraction, we conducted frequentist random-effects dose-response meta-analyses. We assessed risk of bias among included studies using a revision of the Cochrane Risk of Bias 2.0 tool, and the certainty of evidence using GRADE.

Results: We identified 10 RCTs including 2608 patients. Compared to placebo, gefapixant (45 mg BID) probably reduces 24-hour cough frequency (15.97% relative reduction [95% CI: 9.52% to 22.12%]; moderate certainty), awake cough frequency (17.30% relative reduction [95% CI: 10.42% to 23.66%]; moderate certainty), cough severity on a 100-mm VAS (mean difference: 6.11-mm lower [95% CI: 3.63 to 8.61 lower]; moderate certainty), and may improve cough quality of life on the LCQ (1.07 points higher [95% CI: 0.62 to 1.52 higher]; low certainty). Compared to placebo, gefapixant (45 mg BID) probably also increases taste-related adverse events (31 more per 100 patients [95% CI: 21 to 45 more]; moderate certainty).

Conclusions: At 45 mg BID, gefapixant remains efficacious but causes taste-related adverse events.