TY - JOUR
T1 - Adjuvant immunotherapy in renal cell carcinoma
T2 - a systematic review and meta-analysis
AU - Riveros, Carlos
AU - Huang, Emily
AU - Ranganathan, Sanjana
AU - Klaassen, Zachary
AU - Rini, Brian
AU - Wallis, Christopher J.D.
AU - Satkunasivam, Raj
N1 - Publisher Copyright:
© 2023 BJU International.
PY - 2023/5
Y1 - 2023/5
N2 - Objectives: To synthesise available data regarding the disease-free survival (DFS) benefit of adjuvant immune checkpoint inhibitors (ICIs) for patients with renal cell carcinoma (RCC) and evaluate the overall safety profile of ICIs in this setting. Materials and Methods: We utilised PubMed, Embase, and relevant conference proceedings to identify phase III randomised controlled trials comparing adjuvant ICIs vs placebo/observation for RCC. The primary outcome of interest was DFS. Variables for subgroup analyses were programmed death-ligand 1 (PD-L1) expression, sarcomatoid features, nephrectomy type, and disease-risk category. Secondary outcomes included Grade ≥3 adverse events (AEs), immune-related AEs, and treatment discontinuation due to AEs. All outcomes were analysed using random-effects models owing to inter-study heterogeneity. 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 (hazard ratio [HR] 0.85, 95% confidence interval [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) and sarcomatoid features (HR 0.59, 95% CI 0.38–0.91). Conclusion: The evidence base to date regarding ICIs as adjuvant therapy in RCC is mixed – conclusions are limited by considerable heterogeneity between studies. However, pooled analyses suggest that patients with positive PD-L1 expression or sarcomatoid features are most likely to benefit from adjuvant immunotherapy.
AB - Objectives: To synthesise available data regarding the disease-free survival (DFS) benefit of adjuvant immune checkpoint inhibitors (ICIs) for patients with renal cell carcinoma (RCC) and evaluate the overall safety profile of ICIs in this setting. Materials and Methods: We utilised PubMed, Embase, and relevant conference proceedings to identify phase III randomised controlled trials comparing adjuvant ICIs vs placebo/observation for RCC. The primary outcome of interest was DFS. Variables for subgroup analyses were programmed death-ligand 1 (PD-L1) expression, sarcomatoid features, nephrectomy type, and disease-risk category. Secondary outcomes included Grade ≥3 adverse events (AEs), immune-related AEs, and treatment discontinuation due to AEs. All outcomes were analysed using random-effects models owing to inter-study heterogeneity. 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 (hazard ratio [HR] 0.85, 95% confidence interval [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) and sarcomatoid features (HR 0.59, 95% CI 0.38–0.91). Conclusion: The evidence base to date regarding ICIs as adjuvant therapy in RCC is mixed – conclusions are limited by considerable heterogeneity between studies. However, pooled analyses suggest that patients with positive PD-L1 expression or sarcomatoid features are most likely to benefit from adjuvant immunotherapy.
KW - #KidneyCancer
KW - #kcsm
KW - #uroonc
KW - adjuvant
KW - disease-free survival
KW - immunotherapy
KW - renal cell carcinoma
KW - safety
UR - http://www.scopus.com/inward/record.url?scp=85149331226&partnerID=8YFLogxK
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U2 - 10.1111/bju.15981
DO - 10.1111/bju.15981
M3 - Review article
C2 - 36709462
AN - SCOPUS:85149331226
VL - 131
SP - 553
EP - 561
JO - BJU International
JF - BJU International
SN - 1464-4096
IS - 5
ER -