University of Toledo, Toledo, OH
Rabbia Siddiqi , Gaurav Kumar , Hafsah Ijaz , Syed Arsalan Ahmed Naqvi , Ahsan Ayaz , Zaryab Bin Riaz , Alan Haruo Bryce , Thai Huu Ho , Irbaz Bin Riaz , Parminder Singh
Background: Sarcomatoid mRCC exhibits poor prognosis and limited response to vascular endothelial growth factor pathway inhibition. Therefore, we assessed the efficacy of ICI combination therapy in this patient population using data from contemporary trials. Methods: MEDLINE and EMBASE were searched to identify phase III randomized controlled trials (RCTs) comparing the efficacy of ICI combinations with sunitinib monotherapy in patients with sarcomatoid mRCC. Patient important outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and complete response (CR). Precomputed hazard ratios (HR) with 95% confidence intervals (CI) for survival outcomes and binary outcome data for response rates (expressed as relative risk [RR] were meta-analyzed using a DerSimonian-Lairds random-effects method. Mixed treatment comparisons among different ICI combinations were made using a network-meta-analysis within the Bayesian framework. The surface under the cumulative ranking curves (SUCRA) were computed to assess the relative treatment rankings. Results: Six RCTs with a total of 618 patients were considered eligible for inclusion. ICI combination therapy was significantly associated with improved OS (HR: 0.56; 95% CI: 0.43-0.72) and PFS (HR: 0.50; 0.40-0.62), increased ORR (RR: 2.42; 1.92-3.06), and CR (RR: 4.23; 2.00-8.93) when compared to sunitinib in patients with sarcomatoid mRCC (Table). The results were consistent with Hartung-Knapp adjustment. Mixed treatment comparisons using current data revealed no statistically significant differences among different ICI combinations. However, the combination of nivolumab-ipilimumab was consistently ranked higher (rank 2 for OS, ORR, and CR) and may potentially be more efficacious than other counterparts. Conclusions: Current evidence suggests improved survival, delayed disease progression and increased response rates with the use of ICI combination therapy in patients with sarcomatoid mRCC.
Anticipated absolute effects | ||||
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Outcomes | Participants (RCTs) | Relative effect | Risk with Sunitinib | Risk difference with ICI therapy |
Overall survival | 618 (6) | HR 0.56 (0.43-0.72) | 472 per 1000 | 171 fewer per 1000 (from 232 fewer to 103 fewer) |
Progression-free survival | 618 (6) | HR 0.50 (0.40-0.62) | 819 per 1000 | 244 fewer per 1000 (from 324 fewer to 166 fewer) |
Objective response rate | 618 (6) | RR 2.42 (1.92-3.06) | 218 per 1000 | 310 more per 1000 (from 201 more to 450 more) |
Complete response | 569 (5) | RR 4.23 (2.00-8.93) | 24 per 1000 | 77 more per 1000 (from 24 more to 188 more) |
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