Efficacy outcomes with belzutifan versus everolimus by baseline disease characteristics and burden subgroups in the phase 3 LITESPARK-005 study.
Bibliographic record
Abstract
538 Background: At first interim analysis of the randomized, multicenter, open-label, phase 3 LITESPARK-005 study (NCT04195750), belzutifan was associated with a significant and clinically meaningful improvement in progression-free survival (PFS) and objective response rate (ORR) vs everolimus in participants (pts) with advanced clear cell renal cell carcinoma (ccRCC) after both anti–PD-(L)1 and VEGF-targeted therapy. PFS and ORR results remained consistent at final analysis (FA); significant improvement in overall survival (OS) in this heavily pretreated population was not observed. Efficacy outcomes by baseline disease characteristics and tumor burden at FA are presented here. Methods: Pts were aged ≥18 years, had advanced ccRCC, and 1–3 prior systemic regimens (including ≥1 prior PD-[L]1 inhibitor and VEGFR-TKI in combination or in sequence). Belzutifan 120 mg QD or everolimus 10 mg QD were administered to randomized (1:1) pts until disease progression or unacceptable toxicity. An exploratory analysis of PFS and ORR per RECIST 1.1 by central review and OS was conducted in subgroups by bone metastasis (present at baseline, yes vs no), liver metastasis (present at baseline, yes vs no), and baseline tumor burden (sum of diameters of target lesions, < median vs ≥ median). No formal statistical testing was performed. Results: A total of 374 pts were randomized to belzutifan, and 372 to everolimus. At FA (data cutoff: April 15, 2024), median follow-up was 35.8 mo (range 26.9–49.2) for the total population. PFS and ORR benefits with belzutifan vs everolimus were generally consistent with the total population across all analyzed subgroups (Table). In line with the total population at FA, improvement in OS was not observed across most subgroups. Conclusions: Belzutifan is a novel treatment option for patients with advanced ccRCC after prior anti–PD-(L)1 and VEGF-targeted therapies. Exploratory analysis suggests that PFS and ORR benefits with belzutifan vs everolimus are generally consistent across subgroups by baseline disease characteristics and tumor burden. Clinical trial information: NCT04195750 . Bone mets, yes Bone mets, no Liver mets, yes Liver mets, no Sum target lesion diameters,< median Sum target lesion diameters,≥ median Bel Eve Bel Eve Bel Eve Bel Eve Bel Eve Bel Eve N 187 181 187 191 89 103 285 269 174 193 198 171 PFS, median, mo 3.7 4.3 7.0 6.3 4.6 3.7 5.6 5.8 7.3 5.7 4.2 4.8 PFS HR(95% CI) 0.88(0.69–1.11) 0.65(0.51–0.82) 0.55(0.39–0.77) 0.84(0.69–1.02) 0.67(0.52–0.86) 0.80(0.63–1.01) OS, median, mo 15.0 15.1 26.5 23.7 19.1 12.9 21.7 21.8 26.4 26.5 17.3 12.3 OS HR(95% CI) 0.95(0.75–1.20) 0.89(0.69–1.15) 0.63(0.45–0.88) 1.06(0.86–1.30) 0.95(0.73–1.24) 0.76(0.61–0.96) ORR, % 17.6 2.8 27.8 4.2 24.7 3.9 22.1 3.3 28.7 4.1 17.7 2.9 Bel=belzutifan; eve=everolimus; mets=metastasis.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".