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Purpose <p>To assess whether treatment effects in the LUNAR trial are time-varying and to contextualize a single hazard ratio (HR) using complementary, clinically interpretable summaries of when and for how long separation is supported by available information, in a secondary methodological reassessment.</p> Methods <p>Individual patient data were reconstructed by digitalizing published progression-free survival (PFS) Kaplan–Meier (KM) curves. Proportional hazards (PH) were assessed, and treatment effects were summarized using Fleming–Harrington weighted log-rank tests, a piecewise Cox summary, and restricted mean survival time (RMST) at a priori horizons.</p> Results <p>The reconstructed and published KM curves closely matched the trajectories, and the reconstructed Cox HR was consistent with the published HR. PH diagnostics suggested non-proportional hazards (global Schoenfeld test <i>p</i> = 0.001). The early-weighted Fleming–Harrington test showed the strongest separation (χ<sup>2</sup> = 22.0, <i>p</i> &lt; 0.001), whereas the late-weighted test did not provide confirmatory evidence (χ<sup>2</sup> = 2.51, <i>p</i> = 0.110). RMST favored <sup>177</sup>Lu-PSMA plus stereotactic body radiotherapy (relative difference in RMST (%) at 12 and 24 months, 43.7 [95% confidence interval: 24.9–65.3] and 67.8 [33.5–111], respectively). However, late follow-up estimates became increasingly imprecise as risk sets decreased.</p> Conclusion <p>This reconstruction-based, hypothesis-generating reanalysis supported the primary inference of PFS benefit while suggesting time-varying effects. Weighted tests, piecewise summaries, and RMST may provide interpretable complements to a single HR. Late follow-up interpretation remains uncertain because of sparse late risk sets and events.</p>

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Reanalysis of LUNAR progression-free survival using reconstructed individual patient data: time-varying treatment effects

  • 期刊论文

  • 发表日期：

    2026年4月15日

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  • Kenji Tanabe,
  • Soichiro Yoshida,
  • Motohiro Fujiwara,
  • Wei Chen,
  • Shugo Yajima,
  • Hiroyuki Sato,
  • Akihiro Hirakawa,
  • Hiroshi Fukushima,
  • Yosuke Yasuda,
  • Hajime Tanaka,
  • Hitoshi Masuda,
  • Yasuhisa Fujii

摘要

Purpose

To assess whether treatment effects in the LUNAR trial are time-varying and to contextualize a single hazard ratio (HR) using complementary, clinically interpretable summaries of when and for how long separation is supported by available information, in a secondary methodological reassessment.

Methods

Individual patient data were reconstructed by digitalizing published progression-free survival (PFS) Kaplan–Meier (KM) curves. Proportional hazards (PH) were assessed, and treatment effects were summarized using Fleming–Harrington weighted log-rank tests, a piecewise Cox summary, and restricted mean survival time (RMST) at a priori horizons.

Results

The reconstructed and published KM curves closely matched the trajectories, and the reconstructed Cox HR was consistent with the published HR. PH diagnostics suggested non-proportional hazards (global Schoenfeld test p = 0.001). The early-weighted Fleming–Harrington test showed the strongest separation (χ2 = 22.0, p < 0.001), whereas the late-weighted test did not provide confirmatory evidence (χ2 = 2.51, p = 0.110). RMST favored 177Lu-PSMA plus stereotactic body radiotherapy (relative difference in RMST (%) at 12 and 24 months, 43.7 [95% confidence interval: 24.9–65.3] and 67.8 [33.5–111], respectively). However, late follow-up estimates became increasingly imprecise as risk sets decreased.

Conclusion

This reconstruction-based, hypothesis-generating reanalysis supported the primary inference of PFS benefit while suggesting time-varying effects. Weighted tests, piecewise summaries, and RMST may provide interpretable complements to a single HR. Late follow-up interpretation remains uncertain because of sparse late risk sets and events.