Despite not achieving statistical significance, the JAVELIN Renal 101 trial indicated a potentially clinically relevant effect size (hazard ratio [HR], 0.88; 95% confidence interval, 0.75 to 1.04) on overall survival (OS) favoring avelumab plus axitinib over sunitinib for advanced renal cell carcinoma (aRCC). To better interpret these findings, we performed a Bayesian evaluation.
We reanalyzed individual participant data from the JAVELIN Renal 101 trial using a Bayesian framework. Prior distributions were specified for varying levels of enthusiasm and skepticism for avelumab plus axitinib, and a prior from a meta-analysis of similar trials. The posterior probability of any OS benefit with avelumab plus axitinib, Pr(HR < 1.0), and of benefit exceeding the minimal clinically important difference (MCID; HR = 0.75), Pr(HR < MCID), were estimated using Bayesian Cox models. Bayesian hierarchical models evaluated treatment effect heterogeneity across International Metastatic Renal Cell Carcinoma Database Consortium risk groups and programmed death-ligand 1 (PD-L1) status.
Regardless of the prior assumptions used, Pr(HR < 1.0) was consistently high (93.0% to 95.5%). However, Pr(HR < MCID) was low (1.0% to 3.8%). Results were similar when the prior was informed by pooled data from similar trials. In subgroup analyses, Pr(HR < MCID) varied by risk group: 63.4% for poor-risk, 34.9% for favorable-risk, and 0.9% for intermediate-risk aRCC. This probability was low regardless of PD-L1 status.
This exploratory Bayesian reanalysis complements the interpretation of the JAVELIN Renal 101 trial and offers a probabilistic perspective beyond a dichotomous (i.e., significant/nonsignificant) interpretation.
Cancer medicine. 2026 Jun [Epub]
Wataru Fukuokaya, Keiichiro Mori, Takafumi Yanagisawa, Kagenori Ito, Yu Imai, Fumihiko Urabe, Pawel Rajwa, Shahrokh F Shariat, Takahiro Kimura, Akihiro Hirakawa
Department of Urology, The Jikei University School of Medicine, Tokyo, Japan., Department of Urology, Medical University of Silesia, Zabrze, Poland., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Department of Clinical Biostatistics, Graduate School of Medical and Dental Science, Institute of Science Tokyo, Tokyo, Japan.