A Systematic Literature Review (SLR) of Comparative Efficacy Measures in Randomized Controlled Trials (RCTS) of Adjuvant Treatment in Localized Renal Cell Carcinoma (RCC)
Ejzykowicz F1, Kurt M2, Dyer M1, May JR1, Shouman W3, Kasireddy E3, Pourrahmat MM3
1Bristol Myers Squibb, Uxbridge, UK, 2Bristol Myers Squibb, Princeton, NJ, USA, 3Evidinno Outcomes Research Inc., Vancouver, BC, Canada
OBJECTIVES: We conducted an SLR of RCTs to evaluate intermediate and long-term efficacy measures, such as disease-free survival (DFS) and overall survival (OS), for adjuvant treatments in localized RCC.
METHODS: MEDLINE®, Embase, and CENTRAL databases were searched on 01/14/2022 with no publication date limits to identify RCTs evaluating OS and DFS, and endpoints with similar definition to DFS (recurrence-free survival [RFS], progression-free survival [PFS], and event-free survival [EFS]).
RESULTS: Of 4,158 identified records, this SLR included 18 RCTs (published between 1996-2022), 13 of which were phase 3 trials. Across all RCTs, sample size ranged from 46 to 1,943 patients (median=310) and follow-up ranged from 2.0 to 13.7 years (median=6.6 years). Most frequently studied interventions were interferon-alpha (IFN-α; n=3), sunitinib, sorafenib, and fluorouracil + IFN-α + interleukin-2 (n=2 each). Comparisons were against observation (n=10) or placebo (n=8). DFS hazard ratio (HR; n=10) ranged from 0.63 (pembrolizumab vs. placebo) to 1.50 (active specific immunotherapy vs. observation), of which three were significant (pembrolizumab vs. placebo, pazopanib vs. placebo, and sunitinib vs. placebo). RFS HR (n=6) ranged from 0.84 (IFN-α + interleukin-2 vs. observation) to 2.34 (thalidomide vs. observation). PFS HR (n=1) was 1.50 (IFN-α vs. observation) and EFS HR (n=1) was 1.41 (IFN-α vs. observation). HRs were not significant for these intermediate endpoints. OS HR (n=18) ranged from 0.52 (pembrolizumab vs. placebo) to 3.43 (IFN-α vs. observation), and was ≥1 in 10 trials and <1 in 8 trials. OS HR was statistically significant only for fluorouracil + IFN-α + interleukin-2 vs. observation. Age, gender, performance status, and disease histology were the most reported baseline patient characteristics and mostly well-balanced across trials.
CONCLUSIONS: Available evidence base indicated limited intermediate and long-term efficacy for several interventions highlighting the need for novel therapies and can be leveraged to inform surrogacy of DFS and its analogues for OS.
Conference/Value in Health Info
Value in Health, Volume 25, Issue 12S (December 2022)
Clinical Outcomes, Study Approaches
Literature Review & Synthesis, Relating Intermediate to Long-term Outcomes