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
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background and Objective
Adding belzutifan to adjuvant pembrolizumab improved disease-free survival (DFS) in LITESPARK-022, but its durability beyond the 1-year treatment is unknown.
Methods
Following 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 (ΔRMST), hazard ratios (HRs) before and after planned treatment ended, and DFS differences.
Key Findings and Limitations
In LITESPARK-022 (central review), the 24-month ΔRMST was 1.34 months (95% confidence interval 0.73–1.95), and the belzutifan arm remained ahead after month 12 (ΔRMST 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 Implications
Relative 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 Summary
In 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.
