Baseline lactate dehydrogenase (LDH) and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients (pts) treated with everolimus (EVE) versus sunitinib (SUN): Predictive biomarker analysis from the RECORD-3 trial.
Bibliographic record
Abstract
e16118 Background: Data from a randomized mRCC trial of temsirolimus vs interferon reported elevated baseline LDH to be a favorable predictive marker for OS with mTOR inhibitors (Armstrong, JCO 2012). As a product of anaerobic glycolysis, LDH was hypothesized to reflect mTOR activation in tumor cells. We explored this association in the RECORD-3 trial, which randomly assigned untreated pts to the mTOR inhibitor EVE vs the VEGFR TKI SUN without difference in OS (Knox, ASCO 2015). Methods: Pts were grouped by baseline LDH (low, ≤1×ULN; high, > 1×ULN). Treatment arms were stratified by MSKCC risk group. Cox proportional hazards and log-rank tests were used to test the association of LDH category with OS and progression-free survival (PFS). Correlation between LDH category and genomically defined subgroups (somatic mutations in BAP1 or PBRM1, both commonly altered in RCC with reported effects on OS for EVE-treated pts) was tested using Fisher exact test. Results: Among 468 randomly assigned pts, 13% were LDH high and 87% LDH low, with a median of 0.73×ULN (range, 0.15-10.54×ULN). High baseline LDH adversely affected OS for pts receiving EVE (HR 2.96; P< .0001) but showed no association for those receiving SUN (HR 1.18; P= .09). When comparing outcomes with first-line EVE vs SUN, OS was shorter for EVE in LDH-high pts but was not different in LDH-low pts. Associations between LDH and PFS were seen for EVE (HR 2.3; P< .0001) but not for SUN (HR 1.04; P.33). No statistically significant association was seen between LDH category and mutation status of BAP1 (P= .54) or PBRM1 (P= .47). Conclusions: Elevated baseline LDH correlated adversely with PFS and OS for first-line EVE but not SUN. Notably, this predictive effect for EVE is opposite that previously reported in the randomized trial for the mTOR inhibitor temsirolimus vs interferon. Clinical trial information: NCT00903175.Comparison Within HR for OS 95% CI for HR Log-Rank P LDH high vs low EVE arm 2.96 1.83 4.77 < .0001 LDH high vs low SUN arm 1.18 0.71 1.95 .0932 EVE vs SUN LDH low 0.96 0.75 1.24 .4036 EVE vs SUN LDH high 2.42 1.32 4.43 .0024
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".