JCO clinical cancer informatics · 2026
Bayesian Methods for Subgroup Efficacy and Safety: Application to Japanese Patients in JAVELIN Renal 101.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Fukushima Hiroshi, Yoshida Soichiro, Yajima Shugo, Chen Wei, Sato Hiroyuki, Hirakawa Akihiro, Fujiwara Motohiro, Arita Yuki, Yasuda Yosuke, Tanaka Hajime, Masuda Hitoshi, Fujii Yasuhisa
Аннотация
PURPOSE: JAVELIN Renal 101 revealed that avelumab plus axitinib improved progression-free survival (PFS) compared with sunitinib in advanced renal cell carcinoma. However, Japanese subgroup estimates were imprecise. In this study, we evaluated how Bayesian borrowing assumptions translate into posterior probabilities for this subgroup.
PATIENTS AND METHODS: Using published summary data from JAVELIN Renal 101, we modeled PFS on the log hazard-ratio scale with a normal-normal framework, comparing a weakly informative neutral prior with informative borrowing priors centered on the global final estimate (with sensitivity to the third interim estimate). Outputs were posterior HRs, 95% credible intervals (CrIs), P(hazard ratio [HR] <1), and P(HR < 0.8). Sensitivity analyses evaluated alternative borrowing specifications. Adverse events (AEs) were assessed with a no-borrowing beta-binomial framework using noninformative Jeffreys priors for Japanese and global data sets, reporting Japanese posterior means, 95% CrIs, and probabilities of enrichment for any grade and grade ≥3.
RESULTS: Under the neutral prior, evidence for PFS benefit in the Japanese subgroup was moderate (P[HR < 1] = .83; P[HR < 0.8] = .64), whereas informative borrowing priors yielded substantially higher probabilities. Borrowing in PD-L1+ Japanese patients narrowed CrIs while preserving the favorable direction of effect. Any-grade AEs in Japanese patients were most often enriched in hepatic/laboratory, thyroid, infusion-related, and hand-foot domains. For grade ≥3, enrichment mainly involved hepatic/laboratory abnormalities, while rare severe events yielded imprecise posteriors.
CONCLUSION: A paired Bayesian strategy, graded priors for efficacy and no-borrowing priors for safety, produced transparent posterior probability summaries for the Japanese subgroup. This framework illustrates how borrowing can narrow uncertainty when exchangeability is plausible, while clarifying toxicity domains that may warrant closer monitoring, using published trial data.
PATIENTS AND METHODS: Using published summary data from JAVELIN Renal 101, we modeled PFS on the log hazard-ratio scale with a normal-normal framework, comparing a weakly informative neutral prior with informative borrowing priors centered on the global final estimate (with sensitivity to the third interim estimate). Outputs were posterior HRs, 95% credible intervals (CrIs), P(hazard ratio [HR] <1), and P(HR < 0.8). Sensitivity analyses evaluated alternative borrowing specifications. Adverse events (AEs) were assessed with a no-borrowing beta-binomial framework using noninformative Jeffreys priors for Japanese and global data sets, reporting Japanese posterior means, 95% CrIs, and probabilities of enrichment for any grade and grade ≥3.
RESULTS: Under the neutral prior, evidence for PFS benefit in the Japanese subgroup was moderate (P[HR < 1] = .83; P[HR < 0.8] = .64), whereas informative borrowing priors yielded substantially higher probabilities. Borrowing in PD-L1+ Japanese patients narrowed CrIs while preserving the favorable direction of effect. Any-grade AEs in Japanese patients were most often enriched in hepatic/laboratory, thyroid, infusion-related, and hand-foot domains. For grade ≥3, enrichment mainly involved hepatic/laboratory abnormalities, while rare severe events yielded imprecise posteriors.
CONCLUSION: A paired Bayesian strategy, graded priors for efficacy and no-borrowing priors for safety, produced transparent posterior probability summaries for the Japanese subgroup. This framework illustrates how borrowing can narrow uncertainty when exchangeability is plausible, while clarifying toxicity domains that may warrant closer monitoring, using published trial data.