Prognostic and predictive importance of body mass index and type 2 diabetes in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma
Bibliographic record
Abstract
Background Metabolic conditions, such as obesity and type 2 diabetes mellitus (T2DM), cause changes in immune function that may influence immunotherapy effectiveness and immune-related adverse events (irAEs). Objectives To investigate the prognostic and predictive effects of BMI and T2DM and investigate the effect of BMI on toxicity using data from the EORTC 1325/KEYNOTE-054 randomised controlled trial. Methods Pembrolizumab (n = 514) was administered every three weeks for 1 year and prolonged recurrence-free survival (RFS) compared to placebo (n = 505) among patients with resected high-risk stage III melanoma. Here, we used multivariate Cox regression to investigate associations of BMI and T2DM with RFS, and Fine and Gray regression to investigate the association of BMI with the cumulative incidence of irAEs. Results BMI had an approximately U-shaped association with RFS (p = 0.004) in both treatment arms combined. The RFS hazard ratios (HR)s for BMIs of 20, 30 and 35 kg/m 2 (compared to 25 kg/m 2 ) were 1.28 (95 % CI 1.05–1.56), 0.96 (95 % CI 0.88–1.06) and 1.14 (95 % CI 0.98–1.34), respectively. There was no evidence that BMI was associated with pembrolizumab effectiveness (p = 0.20) or the cumulative incidence of irAEs (p = 0.74). T2DM was not associated with RFS (HR 1.01, 95 % CI 0.73–1.40) in both arms combined and there was no evidence of an association between T2DM and pembrolizumab effectiveness (p = 0.83). In summary, in patients with resected high-risk stage III melanoma, BMI was associated with RFS in patients overall and within each treatment group. Conclusions BMI appeared to confer a prognostic effect but was not predictive of pembrolizumab effectiveness regarding RFS. BMI was not related to irAEs among patients receiving pembrolizumab, while T2DM was not associated with RFS irrespective of treatment.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".