Impact of primary tumor location on efficacy and safety of pembrolizumab (pembro) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) enrolled in the phase 2 KEYNOTE-052 and phase 3 KEYNOTE-045 trials.
Bibliographic record
Abstract
516 Background: Pembro showed antitumor activity in 1L and 2L for pts with UC in the single-arm, phase 2 KEYNOTE-052 study (NCT02335424) and the randomized phase 3 KEYNOTE-045 (NCT02256436) study, respectively. This post hoc exploratory analysis evaluated whether primary tumor location affected efficacy and safety of pembro (KEYNOTE-052; KEYNOTE-045) and chemotherapy (chemo; KEYNOTE-045). Methods: KEYNOTE-052 enrolled cisplatin-ineligible pts with advanced/metastatic UC who had not previously received systemic therapy; they received pembro (200 mg IV Q3W). KEYNOTE-045 enrolled pts with advanced/metastatic UC who had received platinum-containing chemo; pts were randomly assigned 1:1 to receive pembro (200 mg IV Q3W) or investigator’s choice of chemo (paclitaxel, docetaxel, or vinflunine). Both studies required pts to have measurable disease per RECIST v1.1. Upper tract (UT) UC included primary tumors in the renal pelvis or ureter; lower tract (LT) UC included primary tumors in the bladder or urethra. Pts with UT and LT disease (UT/LT) were classified as LT. Pts receiving pembro were treated until disease progression, unacceptable toxicity, or withdrawal of consent, for up to 2y. End points were PFS, ORR, and DOR per RECIST v1.1 by central radiology assessment and OS. Results: A total of 369 pembro-treated pts (68 UT; 301 LT [79 UT/LT]) from KEYNOTE-052 plus 270 pembro-treated pts (93 UT; 177 LT [33 UT/LT]) and 272 chemo-treated pts (94 UT; 178 LT) from KEYNOTE-045 were evaluated. Median follow-up from randomization to data cutoff (09/26/20 and 10/1/20, respectively) was ≥56 mo. Both studies enrolled a similar percentage of pts with PD-L1–positive tumors (25%-30%). PFS, ORR, DOR, and OS for pembro were consistent regardless of tumor location, although ORR for KEYNOTE-045 was lower for the UT group (Table). In the chemo arm of KEYNOTE-045, similar efficacy was observed regardless of tumor location or regimen. Grade 3-5 TRAEs occurred at similar rates in KEYNOTE-052 (19.1% UT; 21.6% LT) and KEYNOTE-045 (17.2% UT; 16.8% LT). Conclusions: In this exploratory analysis, pembro showed similar clinical activity and manageable safety regardless of primary UC tumor location. Clinical trial information: NCT02256436 and NCT02335424. [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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".