Adjuvant immunotherapy in renal cell carcinoma: a systematic review and meta‐analysis

Abstract

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.

Adjuvant therapy in renal cell carcinoma: Tyrosine kinase inhibitor versus immune checkpoint inhibitor

“…These findings align closely with those from Laukhtina et al, [5] who reported an HR of 0.88 (95% CI 0.81-0.96) for DFS (TKIs vs placebos, P = .004) and a slightly different HR of 0.93 (95% CI 0.83-1.04) for OS (TKIs vs placebos, P = .23). In our study, the HR for DFS in the IMT group was 0.82 (95% CI 0.71-0.94) (DFS: IMTs vs placebos, P = .004), which slightly varies from Riveros et al [6] who reported an HR of 0.81 (95% CI 0.63-1.05) (DFS: IMTs vs placebos, P = .11). It is important to note that IPD meta-analysis and conventional meta-analysis are distinct methods.…”

“…[42][43][44][45] This meta-analysis is, to the best of our knowledge, the first to reconstruct and analyze DFS and OS curves, evaluating the efficacy of adjuvant IMTs and TKIs in RCC patients. It also [9] Serplulimab + CT PD- [8] Adebrelimab [6] Atezolizumab [7] Durvalumab represents the first comprehensive investigation into the serious AEs commonly associated with these 2 treatment strategies, comparing the incidence of severe AEs and the discontinuation rates due to AEs. Our study demonstrates that both adjuvant IMT and TKI therapies offer a slight benefit in DFS for patients undergoing nephrectomy.…”

“…Recent meta-analyses suggest that RCC patients with positive PD-L1 expression or sarcomatoid features are more likely to benefit from adjuvant IMTs. [6] Although prior meta-analyses have indicated that both adjuvant TKIs and IMTs may improve DFS in patients with RCC, no studies have yet directly compared the efficacy of these 2 strategies. Consequently, we have utilized reconstructed individual patient data (IPD) to indirectly compare the effectiveness of these treatment approaches, while also providing a comprehensive summary of the serious adverse events (AEs) associated with these therapies.…”

“…Recent meta-analyses suggest that RCC patients with positive PD-L1 expression or sarcomatoid features are more likely to benefit from adjuvant IMTs. [6]…”

Understanding Factors that Influence Prognosis and Response to Therapy in Clear Cell Renal Cell Carcinoma

“…Among combination therapies, ipilimumab (anti–CTLA-4) combined with nivolumab (anti–PD-1) is the regimen that appears to be associated with the highest chances of long-term disease control 6,7 . In addition, the recent positive results of the Keynote-564 trial led to FDA approval of pembrolizumab (anti–PD-1) in the adjuvant setting; however, 3 other studies have failed to show similar benefits 8,9 …”