Bayesian Analysis to Refine East Asian Subgroup Estimates in the CLEAR Trial (Lenvatinib Plus Pembrolizumab vs. Sunitinib) for Advanced Renal Cell Carcinoma.

BACKGROUND/AIM: This study aimed to refine estimates of lenvatinib plus pembrolizumab (Len/Pembro) efficacy in East Asian patients with advanced renal cell carcinoma (aRCC) in the CLEAR trial using Bayesian borrowing from Western Europe and North America (WENA), and to assess safety while preserving region-specific toxicity.

MATERIALS AND

METHODS

Published hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) in WENA and East Asian subgroups were reanalyzed using Bayesian normal models (priors: neutral to strong borrowing). Posterior HRs, 95% credible intervals (CrIs), and benefit probabilities were derived. Adverse events (AEs) in East Asian (n=75) versus non-East Asian (n=277) patients were assessed with independent Beta-Binomial models with Jeffreys priors to estimate posterior incidences and probabilities of excess toxicity.

RESULTS

The observed East Asian PFS HR was 0.38 (95% CI=0.23-0.62), similar to the WENA HR of 0.49 (95% CI=0.37-0.64). Bayesian borrowing yielded posterior PFS HRs of 0.40-0.46 with narrower CrIs and >99% probability of benefit. For OS, East Asian data alone were imprecise (HR= 0.71, 95% CI=0.30-1.71), but borrowing from WENA (HR=0.78, 95% CI=0.57-1.05) gave posterior HRs 0.75-0.77; under strong borrowing 0.77 (95% CrI=0.58-1.03) with 96% probability. East Asians showed excess toxicity for any-grade and grade ≥3 proteinuria and hand-foot syndrome, with signals for hypothyroidism, dysphonia, and stomatitis.

CONCLUSION

Bayesian information borrowing demonstrates a clear progression-free survival benefit and supports a credible overall survival advantage for first-line lenvatinib plus pembrolizumab in East Asian patients with advanced renal cell carcinoma. Independent safety modeling identified a distinct regional pattern of higher VEGFR-related toxicities, emphasizing the need for proactive toxicity management in this population.