Clinical characteristics and determinants of primary refractory metastatic renal cell carcinoma (mRCC): An International Metastatic Database Consortium (IMDC) study.
Bibliographic record
Abstract
4549 Background: Immune checkpoint inhibitor (ICI)-based regimens, including ICI + ICI and ICI+VEGF-targeted therapy (VEGF-TT), represent the current standard of care for first line (1L) in mRCC. A subset of patients (pts) experiences primary refractory disease, defined as progressive disease (PD) as best response. The aim of this study is to investigate the clinical characteristics and determinants of pts with primary refractory mRCC. Methods: Pts with mRCC treated with 1L ICI-based regimens from the IMDC were included. Pts were categorized as primary refractory (PD as best response evaluated per RECIST 1.1 criteria) and non-primary refractory (stable disease or partial/complete response as best response). Baseline characteristics were compared using a Chi-Square test. Independent factors associated with primary refractory mRCC were identified using a logistic regression. Results: In total, 2001 pts were included, of which 1301 (65%) were treated with dual ICI, and 701 (35%) with ICI+VEGF-TT. Of 2001 pts, 494 (24%) experienced PD at first restaging. Primary refractory and non-primary refractory groups did not differ by age or gender. The primary refractory group had more pts treated with dual ICI (76 vs. 62%), more pts with poor IMDC risk (29 vs. 19%), and more pts with non-clear cell RCC (27 vs. 19%; all p < 0.001). The primary refractory group had shorter diagnosis to treatment interval (mean: 1.6 vs. 2.3 years), lower KPS (median: 80 vs. 90), higher rate of anemia (65% vs. 52%), neutrophilia (11% vs. 9%), and thrombocytosis (30 vs 22%; all p < 0.001). The primary refractory group had more liver (24 vs. 17%; p < 0.001), bone (39 vs 32%; p < 0.001) and lymph nodes metastasis (52 vs. 47%; p = 0.03) at the start of 1L therapy. On multivariable analysis, independent factors associated with primary refractory RCC were low KPS, and the presence of liver metastasis or bone metastasis (Table). Dual ICI regimen was associated with a 1.8-fold increase of primary refractory RCC. Conclusions: In pts with mRCC, low KPS and the presence of liver or bone metastasis are independent risk factors for the development of primary refractory disease. Primary refractory disease is more commonly observed in pts receiving dual ICI compared to those on ICI+VEGF-TT regimen. Multivariable analysis for independent factors associated with primary refractory RCC. OR Lower 95% CI Upper 95% CI p-value Diagnosis to treatment interval < 1 year (yes vs. no) 1.2 0.9 1.6 0.2 Anemia (yes vs. no) 1.37 1.1 1.8 0.03 Low KPS(<80: yes vs. no) 1.9 1.4 2.5 <0.001 Neutrophilia (yes vs. no) 1.3 1 1.8 0.09 Thrombocytosis (yes vs. no) 0.9 0.7 1.3 0.6 Liver metastasis (yes vs. no) 1.7 1.3 2.3 <0.001 Lymph Nodes metastasis (yes vs. no) 1.3 1 1.6 0.07 Bone metastasis (yes vs. no) 1.3 1.03 1.7 0.03 Dual ICI (vs. ICI+VEGF-TT) 1.8 1.37 2.4 <0.001 Non-clear cell RCC (vs. clear cell) 1.3 1 1.8 0.06 Nephrectomy (yes vs. no) 0.9 0.7 1.2 0.6
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".