Adjuvant immunotherapy in renal cell carcinoma: A systematic review and meta-analysis of randomized clinical trials.

Abstract

671 Background: There has been interest in adjuvant immune checkpoint inhibition (ICI) following surgical resection in patients with high-risk renal cell carcinoma (RCC) given high recurrence rates and approvals of ICI in metastatic RCC. The primary objective of this analysis was to synthesize available data regarding the disease-free survival (DFS) benefit of adjuvant ICIs for patients with RCC. Methods: This systematic review was performed according to the PRISMA guidelines. The protocol was registered in PROSPERO (CRD42022361599). We searched PubMed, EMBASE, and relevant conference proceedings to identify phase III randomized controlled trials (RCTs) comparing adjuvant ICI versus placebo/observation. The primary outcome of interest was DFS. Results: Among the four included studies, one demonstrated a significant DFS benefit. There was considerable clinical and statistical heterogeneity (I2=64%) due to differences in inclusion criteria and interventions. While pooled results across the four studies did not demonstrate a significant benefit in DFS overall (HR 0.85, 95% CI 0.69-1.04), there was significant benefit among patients with positive PD-L1 expression (HR 0.72, 95% CI 0.55-0.94) or sarcomatoid features (HR 0.59, 95% CI 0.38-0.91). Conclusions: The evidence base to date regarding ICI as adjuvant therapy in RCC is mixed – conclusions are limited by considerable heterogeneity between studies. However, pooled analyses suggest that patients with positive PDL1 expression or sarcomatoid features are most likely to benefit from adjuvant immunotherapy.

2023 American Society of Clinical Oncology Genitourinary (ASCO-GU) Cancers Symposium

“…Two systematic reviews summarized the current landscape of immunotherapy trials. 14,15 Of the four phase-3 trials (CheckMate 914, IMmotion 010, KEYNOTE 564, and PROSPER), only KEYNOTE 564 showed an improvement in recurrence-free survival (RFS) in the immunotherapy arm (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.50-0.79). The pooled analysis revealed that most of the inconsistencies were due to variability between trials, and the pooled decrease in recurrence risk was 15% (pooled HR 0.85, 95% CI 0.69-1.04).…”