Association of time to second-line (2L) immune-checkpoint inhibitors (ICI) and outcomes with ICIs in patients (pts) with advanced urothelial carcinoma (aUC).
Bibliographic record
Abstract
505 Background: Current standard therapy for most pts with aUC is first-line (1L) platinum-based chemotherapy followed by ICI maintenance (or 2L if progression). Shorter time on 1L or between therapy lines may be a surrogate of more aggressive disease and poor outcome, but its prognostic role in ICI response is unclear. We hypothesized that shorter time until start of 2L ICI would be associated with worse outcomes in aUC. Methods: We performed a retrospective multi-institution cohort study in pts with aUC treated with 1L platinum-based chemotherapy, who later received 2L ICI. Pts receiving maintenance ICI were excluded. We calculated the time from start of 1L platinum chemotherapy to start of 2L ICI, dichotomizing the exposure into ≤6 months and >6 months. We compared overall response rate (ORR) to 2L ICI, progression-free survival (PFS) and overall survival (OS) from the start of 2L ICI between the two populations. ORR was compared among groups using multivariable logistic regression and PFS, OS using cox regression. Analysis was adjusted for calculated Bellmunt score. Results: From a total of 1283 pts, 462 received 1L platinum chemotherapy; among those, 350 received 2L ICI. After exclusions, 270, 269 and 260 pts were included in the ORR, PFS and OS analyses, respectively. Median age was 70 years, 78% men, 75% White, 74% with pure urothelial histology, 21% upper tract, 60% received cisplatin in 1L. Pts with time to 2L ICI ≤6 months had significantly higher Bellmunt scores (32% vs 22% score=2, 9% vs 3% score=3). ORR and PFS were comparable between pts with ≤ and >6 months to 2L ICI. However, OS was significantly longer for pts with >6 months to 2L ICI (median [m]OS 13 vs 7 months, p=0.002), (Table). Conclusions: Among pts with aUC treated with 2L ICI, time to 2L ICI ≤6 months from 1L platinum based chemotherapy was associated with similar ORR and PFS but shorter OS. Limitations include retrospective nature, patient selection, confounding factors. More studies are needed on the impact of platinum resistance in pts with aUC treated with ICIs.[Table: see text]
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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 | 0.000 | 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 | 0.001 |
| 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".