Adjuvant Systemic Therapies After Nephrectomy for Renal Cell Carcinoma: A Bayesian Network Meta-Analysis and...

Adjuvant pembrolizumab has improved disease-free survival after nephrectomy for high-risk renal cell carcinoma, and pembrolizumab plus belzutifan has further expanded the treatment landscape.

We compared efficacy and treatment burden across adjuvant systemic therapies and examined the benefit-risk trade-off of the combination.

Randomized trials of systemic therapy after nephrectomy were synthesized using a Bayesian network meta-analysis. Disease-free survival hazard ratios were converted to illustrative 2-year estimates using a common pembrolizumab baseline. Observed differences in 2-year disease-free survival, grade 3 or higher adverse events, and treatment discontinuation came from LITESPARK-022. Using these data, a multi-criteria decision analysis examined how outcome weighting affected the balance between the two regimens.

Six randomized datasets formed a tree-shaped network of eight regimens. In LITESPARK-022, adding belzutifan yielded approximately seven additional disease-free patients per 100 treated, but also approximately 22 additional patients with grade 3 or higher adverse events and 15 additional treatment discontinuations. Under the primary decision-analytic assumptions, the combination had the higher net-benefit score only when disease-free survival received roughly two thirds of the decision weight (threshold 0.68; range 0.47-0.79 across sensitivity analyses). Most comparisons relied on a single dataset, and overall survival and patient-reported outcomes remained immature.

Adding belzutifan to pembrolizumab improved disease-free survival but increased toxicity and treatment discontinuation. The decision analysis illustrates a model-dependent trade-off rather than identifying a preferred regimen. Because overall survival data are immature, the decision to intensify treatment remains risk and preference sensitive.

CRD420261454205.