Real-world assessment of clinical outcomes of first-line treatment in metastatic papillary renal cell carcinoma.
Bibliographic record
Abstract
471 Background: Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC) representing up to 15% of RCC. First line (1L) phase II trials have evaluated immunotherapy (IO) in combination with IO or tyrosine kinase inhibitors (TKI) in nccRCC, but these cohorts are heterogeneous, with few comparative results. Therefore, the specific value of IO therapy for pRCC remains unquantified. Methods: We conducted an analysis based on prospectively collected data from the Canadian Kidney Cancer information system (CKCis) database. The objective was to evaluate efficacy of 1L systemic therapy of metastatic pRCC with either IO based or VEGFR-TKI. Baseline characteristics, treatment outcome and safety were collected. Primary endpoint was time-to-treatment failure (TTF). Secondary endpoints included overall survival (OS), objective response rate (ORR), adverse events requiring a change in dose/schedule (TRAEs). TTF, OS and ORR were adjusted (adj) for IMDC risk groups. Results: Between 01/2011 to 01/2024,206 pRCC pts were treated: 70 on IO single agent or in combination IO-IO/IO-TKI and 136 with TKI monotherapy. The median follow-up was 20.6 months (mo) (range: 1.6-146.1). There were no significant differences in baseline characteristics between 2 groups, described in table. The median TTF with IO was 9.8 mo (95%CI: 4.5, 15.9) versus (vs) 5.7 mo with TKI (95%CI: 4.6, 8.1) (adj HR: 0.61 [0.42-0.89] p=0.01). The median OS was 36.9 mo with IO (95%CI: 26.5, not reached (NR)) vs 21.6 mo with TKI (95%CI: 18, 27.9) (adj HR: 0.51 [0.3-0.85], p=0.009). Among the 170 evaluable pts, ORR was 37% (95% CI: 24.2-49.9) with IO and 21.5% (95% CI: 14.1-29) with TKI (adj OR: 2.4 [1.0-5.6] p=0.04). The TKI-IO subgroup had better TTF and OS compared to TKI therapy, with 16.9 mo (95%CI: 5.5-22.6) (adj HR: 0.46 [0.26-0.82] p=0.009), and NR (95%CI: 18.9-NR) (adj HR: 0.24 [0.08-0.78] p=0.02) respectively. 28% of pts discontinued treatment. TRAEs of grade 3-5 were noted in 27% in IO group and in 73% in TKI group. Conclusions: This study presents comparative data on 1L treatment metastatic pRCC. It shows an improved TTF and OS in the IO group, particularly in TKI-IO treated pts. Our findings underline the need for further clinical trials evaluating 1L IO in pts with metastatic pRCC. Baseline characteristics. Overall cohortn = 206 IO treatmentn = 70 (34%) TKI treatmentn = 136 (66%) Median age (range) 67 (30-89) 69 67 Sex Male 162 (79%) 51 (73%) 111 (82%) IMDC score Favorable Intermediate Poor Unknown 31 (20%)93 (60%)30 (19.5%)52 15 (29%)30 (58%)7 (13%)18 16 (16%)63 (62%)23 (22%)34 Prior Nephrectomy 164 (80%) 56 (80%) 108 (79%) Sarcomatoid component 12 (8%) 5 (7%) 7 (5%) Therapy Nivolumab + ipilimumab Pembrolizumab + axitinib Pembrolizumab + lenvatinib Pembrolizumab Nivolumab Sunitinib Pazopanib Cabozantinib Crizotinib Savolitinib m-Tor inhibitors 27 (13%)23 (11%)7 (3.5%)11 (5%)2 (1%) 88 (43%)20 (10%)8 (4%)3 (1.5%)7 (3.5%)9 (4.5%)
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Observational | low |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Observational | low |
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 | 0.008 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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, unvalidatedLabeled directly by 2 models reading the full record.
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".