Real-world assessment of clinical outcomes of first-line treatment in metastatic papillary renal cell carcinoma
Bibliographic record
Abstract
BACKGROUND: Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC), representing up to 15% of RCC cases. Phase 2 trials have evaluated first-line (1L) immunotherapy (IO)-based treatment in nccRCC, but with heterogeneous cohorts and limited comparative data. The specific value of IO for metastatic pRCC (mpRCC) remains unquantified. METHODS: We analyzed prospectively collected data from the Canadian Kidney Cancer Information System to assess the efficacy of 1L systemic therapy in mpRCC with IO-based regimens vs tyrosine kinase inhibitors (TKI). The primary endpoint was time-to-treatment failure (TTF). Secondary endpoints included overall survival (OS), objective response rate (ORR), and treatment-related adverse events (TRAEs). Analyses were adjusted (adj) for IMDC risk groups. RESULTS: From 2011 to 2024, 197 mpRCC patients received 1L therapy: 70 with IO (alone or in combination) and 127 with TKI. Median follow-up was 21.6 months. Median TTF was 9.9 months with IO vs 5.9 months with TKI (adjHR: 0.62 [0.43-0.91], P = .01). Median OS was 36.9 months with IO vs 23.2 months with TKI (adjHR: 0.54 [0.3-0.9], P = .018). Objective response rate was 37% with IO vs 23% with TKI (adjOR: 2.2 [0.95-5.2], P = .07). The TKI-IO subgroup showed the longest TTF (16.9 months, adjHR: 0.47 [0.26-0.85], P = .01) and OS (not reached, adjHR: 0.26 [0.08-0.83], P = .02), compared to TKI. Grade 3-5 TRAEs occurred in 31% (IO) vs 27% (TKI). CONCLUSIONS: This real-world study highlights the benefit of IO-based treatment in mpRCC, particularly in the TKI-IO subgroup. Our findings may inform further trials evaluating 1L IO in mpRCC.
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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) | 0.001 | 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".