Enfortumab vedotin (EV) with pembrolizumab (P) versus chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC): Analysis of the cisplatin (cis)-ineligible population from EV-302/KEYNOTE-A39.
Bibliographic record
Abstract
4563 Background: EV-302/KEYNOTE-A39 (NCT04223856) is a phase 3, randomized, open-label, global study comparing EV+P with platinum-based chemo (PBC) for first-line (1L) treatment (tx) of patients (pts) with la/mUC regardless of cis eligibility. In EV-302, EV+P demonstrated a statistically significant and clinically meaningful benefit compared with PBC for the dual primary endpoints of PFS (hazard ratio [HR]: 0.45; P<0.00001) and OS (HR: 0.47; P<0.00001) in the overall pt population (Powles ESMO 2023), reducing the risk of progression and/or death by more than 50%. EV+P was FDA-approved in Dec 2023 for tx of adults with la/mUC. As cis eligibility status has long defined 1L tx, here we present results of an analysis for pts who were ineligible for cis at randomization. Methods: Pts with previously untreated la/mUC were randomized 1:1 to receive 3-week cycles of EV (1.25 mg/kg IV; Days 1 and 8) and P (200 mg IV; Day 1) or PBC (gemcitabine with cis or carboplatin [carbo]). Select secondary endpoints included confirmed objective response rate (ORR), duration of response (DOR), and safety. Pts were deemed eligible/ineligible for cis following protocol-defined criteria and stratified accordingly. Results: 408 pts (EV+P: 198, PBC: 210) were cis-ineligible at randomization. 205 (97.6%) pts in the PBC arm received carbo at Cyle 1. mPFS was 10.6 months for EV+P; 6.1 months for PBC (HR: 0.43, 95% CI, 0.33, 0.55). mOS was not reached for EV+P and was 12.7 months for PBC (HR: 0.43, 95% CI, 0.31, 0.59). ORR for EV+P was 63.9% with 24.7% complete response (CR) rate; mDOR (95% CI) was not reached (16.3 months, NR). ORR for PBC was 34.9% with 9.1% CR rate; mDOR (95% CI) was 6.6 months (5.6, 10.2). In EV+P arm, 62 pts (31.3%) remained on tx at data cutoff (DCO). 55 pts (27.8%) received subsequent therapy. 10 pts received cis and 27 pts received carbo as first subsequent therapy. In PBC arm, all were off study tx at DCO. 114 pts (54.3%) received any PD-1/L1 therapy following PBC. 52 pts received maintenance avelumab; 58 pts received PD-1/L1 therapy as second-line tx. Grade ≥3 TRAEs occurred in 58.4% of pts with EV+P and 77.1% of pts with PBC. Most common grade ≥3 TRAEs of special interest for EV were skin reactions (16.2%), peripheral neuropathy (8.1%), and hyperglycemia (4.1%). Most common grade ≥3 tx-emergent AEs of special interest for P were severe skin reaction (14.7%), hepatitis (2.0%), and pneumonitis (2.0%). Conclusions: In this pt population with historically poor prognosis, EV+P improved clinical outcomes in pts who were ineligible for cis; results were consistent with the overall population. The risk of death was reduced by more than 50%. The AE profile of EV+P was generally manageable with no new safety signals. The results of EV-302 support EV+P as a new SOC for la/mUC, including pts who are ineligible for cis. Clinical trial information: NCT04223856 .
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".