Pembrolizumab (pembro) versus investigator’s choice of paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC): 5-year follow-up from the phase 3 KEYNOTE-045 trial.
Bibliographic record
Abstract
4532 Background: Pembro was approved for the treatment of locally advanced or metastatic UC that progressed during or after a platinum-containing regimen, based on the phase 3 KEYNOTE-045 (NCT02256436) trial that showed significantly improved OS with use of pembro. Updated results are presented from KEYNOTE-045 after >5 y of follow-up since the last patient (pt) was randomized. Methods: KEYNOTE-045 is a randomized, multisite, open-label, phase 3 trial. Pts with histologically or cytologically confirmed UC, progression after platinum-containing chemo, ECOG PS 0-2, measurable disease per RECIST v1.1, and ≤2 prior lines of systemic therapy were eligible. Pts were randomly assigned 1:1 to receive pembro 200 mg Q3W or investigator’s choice of paclitaxel 175 mg/m 2 Q3W, docetaxel 75 mg/m 2 Q3W, or vinflunine 320 mg/m 2 Q3W. Primary end points are PFS (RECIST v1.1, blinded central review) and OS. ORR and duration of response (DOR) were key secondary end points. Results: As of Oct 1, 2020, among 542 enrolled pts, median time from randomization to data cutoff was 62.9 mo (range 58.6-70.9). 9.4% and 0% of pts in the pembro and chemo arms, respectively, completed 2 years of therapy. Median OS was longer for pembro vs chemo (10.1 vs 7.2 mo; HR, 0.71 [95% CI, 0.59-0.86]) overall and in pts with CPS ≥10 (8.0 vs 4.9 mo; HR, 0.59 [95% CI, 0.40-0.86]). For pts with CR or PR, median OS was not reached and 16.4 (95% CI, 11.3-25.1) mo in the pembro and chemo arms, respectively (Table). OS rates at 48 mo were 16.7% for pembro and 10.1% for chemo; 60-mo OS rates were 14.9% and 8.7%, respectively. OS benefit with pembro vs chemo continued regardless of age, ECOG PS, prior therapy, liver metastases, baseline hemoglobin, time from last chemo, histology, risk factors, and chemo choice. Median DOR for responders was longer for pembro vs chemo (29.7 mo [1.6+ to 60.5+] vs 4.4 mo [1.4+ to 63.1+]), and a greater proportion of responses lasted ≥48 mo (40.9% vs 28.3%, Kaplan-Meier) and ≥60 mo (32.8% vs 28.3%). ORR was higher for pembro vs chemo (21.9% vs 11.0%; difference 10.8% [95% CI, 4.6-17.0]). Fewer pts given pembro vs chemo experienced a treatment-related AE of any grade (62.0% vs 90.6%) or grade ≥3 (16.9% vs 50.2%). Conclusions: After 5 y, pembro maintained clinically meaningful OS benefit vs chemo in pts with locally advanced or metastatic UC that progressed during or after platinum-based chemo. Pts who responded to pembro experienced a durable response (median >2 y). Clinical trial information: NCT02256436 .[Table: see text]
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.005 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".