Does the Disease-free Survival Benefit of Adding Belzutifan to Adjuvant Pembrolizumab Persist Beyond the Planned Treatment Period? A Reconstructed Individual Patient Data Analysis of Phase 3 Renal Cell Carcinoma Trials
- 1Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Abstract
Background and ObjectiveAdding belzutifan to adjuvant pembrolizumab improved disease-free survival (DFS) in LITESPARK-022, but its durability beyond the 1-year treatment is unknown.
MethodsFollowing a registered plan, we reconstructed individual patient data from published Kaplan-Meier curves of ten phase 3 adjuvant renal cell carcinoma trials. Within each trial, we estimated restricted mean survival time differences ({Delta}RMST), hazard ratios (HRs) before and after planned treatment ended, and DFS differences.
Key Findings and LimitationsIn LITESPARK-022 (central review), the 24-month {Delta}RMST was 1.34 months (95% confidence interval 0.73-1.95), and the belzutifan arm remained ahead after month 12 ({Delta}RMST increment 0.74 months/yr, 0.32-1.19). The HR was 0.55 (0.43-0.71) before month 12 and 1.16 (0.87-1.54) afterwards (post/pre ratio 2.10); investigator assessment showed similar attenuation. Similar ratios occurred in KEYNOTE-564 at its first interim analysis (2.02), whose benefit persisted, and in SORCE and PROTECT (2.09, 2.59), whose benefit faded. From months 12 to 30 (post hoc), the DFS difference changed by -3.7 percentage points (-8.1 to 0.8) with central review and 0.6 (-4.0 to 5.0) with investigator assessment. Data were reconstructed, and follow-up was short.
Conclusions and Clinical ImplicationsRelative hazard reductions with belzutifan were greater before month 12; durability of the absolute DFS advantage is uncertain and assessment-dependent, so single-HR projections should be avoided.
Patient SummaryIn a trial after kidney cancer surgery, adding belzutifan to pembrolizumab increased the average time without cancer returning by about 6 weeks over 2 years, but caused more serious side effects. Whether this advantage lasts after treatment ends is not yet clear.
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BibTeX
@misc{chang2026does,
title = {{Does the Disease-free Survival Benefit of Adding Belzutifan to Adjuvant Pembrolizumab Persist Beyond the Planned Treatment Period? A Reconstructed Individual Patient Data Analysis of Phase 3 Renal Cell Carcinoma Trials}},
author = {H.-H. Chang and C.-K. Chang and T.-Y. Tang and J.-H. Jhan and S.-W. Dong and Y.-S. Juan and J.-H. Geng and H.-C. Ou and H.-Y. Lee and C.-Y. Li and H.-C. Yeh and M.-K. Leong and C.-H. Liu and Y.-C. Lee and S.-P. Huang},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.14.26365591},
url = {https://www.medrxiv.org/content/10.64898/2026.10.14.26365591v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Does the Disease-free Survival Benefit of Adding Belzutifan to Adjuvant Pembrolizumab Persist Beyond the Planned Treatment Period? A Reconstructed Individual Patient Data Analysis of Phase 3 Renal Cell Carcinoma Trials
AU - H.-H. Chang
AU - C.-K. Chang
AU - T.-Y. Tang
AU - J.-H. Jhan
AU - S.-W. Dong
AU - Y.-S. Juan
AU - J.-H. Geng
AU - H.-C. Ou
AU - H.-Y. Lee
AU - C.-Y. Li
AU - H.-C. Yeh
AU - M.-K. Leong
AU - C.-H. Liu
AU - Y.-C. Lee
AU - S.-P. Huang
PY - 2026
DA - 2026/10/14
PB - medRxiv
DO - 10.64898/2026.10.14.26365591
UR - https://www.medrxiv.org/content/10.64898/2026.10.14.26365591v1
AB - Background and ObjectiveAdding belzutifan to adjuvant pembrolizumab improved disease-free survival (DFS) in LITESPARK-022, but its durability beyond the 1-year treatment is unknown. MethodsFollowing a registered plan, we reconstructed individual patient data from published Kaplan-Meier curves of ten phase 3 adjuvant renal cell carcinoma trials. Within each trial, we estimated restricted mean survival time differences ({Delta}RMST), hazard ratios (HRs) before and after planned treatment ended, and DFS differences. Key Findings and LimitationsIn LITESPARK-022 (central review), the 24-month {Delta}RMST was 1.34 months (95% confidence interval 0.73-1.95), and the belzutifan arm remained ahead after month 12 ({Delta}RMST increment 0.74 months/yr, 0.32-1.19). The HR was 0.55 (0.43-0.71) before month 12 and 1.16 (0.87-1.54) afterwards (post/pre ratio 2.10); investigator assessment showed similar attenuation. Similar ratios occurred in KEYNOTE-564 at its first interim analysis (2.02), whose benefit persisted, and in SORCE and PROTECT (2.09, 2.59), whose benefit faded. From months 12 to 30 (post hoc), the DFS difference changed by -3.7 percentage points (-8.1 to 0.8) with central review and 0.6 (-4.0 to 5.0) with investigator assessment. Data were reconstructed, and follow-up was short. Conclusions and Clinical ImplicationsRelative hazard reductions with belzutifan were greater before month 12; durability of the absolute DFS advantage is uncertain and assessment-dependent, so single-HR projections should be avoided. Patient SummaryIn a trial after kidney cancer surgery, adding belzutifan to pembrolizumab increased the average time without cancer returning by about 6 weeks over 2 years, but caused more serious side effects. Whether this advantage lasts after treatment ends is not yet clear.
ER -