39MO Phase III ENGOT-En9/LEAP-001 study: Lenvatinib + pembrolizumab (LEN/PEMBRO) vs chemotherapy (chemo) as first-line (1L) therapy for advanced or recurrent endometrial cancer
Bibliographic record
Abstract
LEN/PEMBRO following prior systemic therapy in any setting, including neo/adjuvant, is a standard of care for advanced endometrial cancer (EC). The phase 3 ENGOT-en9/LEAP-001 trial (NCT03884101) compared 1L LEN/PEMBRO vs chemo in patients (pts) with advanced/recurrent EC. Eligible pts had stage III–IV or recurrent, measurable/non-measurable, radiographically apparent EC, with no prior chemo or PD ≥6 mo after neo/adjuvant platinum-based chemo. Pts were randomized 1:1 (stratified by proficient vs deficient mismatch repair status [pMMR/dMMR] and, in the pMMR stratum, by ECOG PS [0/1], measurable disease [yes/no], and chemo/chemoradiation [yes/no]) to lenvatinib 20 mg QD plus pembrolizumab 200 mg Q3W or paclitaxel 175 mg/m2 Q3W plus carboplatin AUC 6 Q3W. Dual primary endpoints were PFS (RECIST v1.1, blinded independent central review) and OS in the pMMR population and among all-comers. Secondary endpoints included ORR and safety; duration of response (DOR) was an exploratory endpoint; and efficacy outcomes assessed by tumor histology was a prespecified exploratory analysis. 842 pts were randomized. At final analysis (data cutoff, 2 Oct 2023), after median follow-up of 38.4 (range, 30.3–52.9) mo, statistical significance for noninferiority (NI) OS endpoint was not achieved for LEN/PEMBRO vs chemo in the pMMR population (HR, 1.02 [95% CI, 0.83–1.26]; NI P = 0.2459875; Table). PFS and OS results for LEN/PEMBRO vs chemo by histological subtype will be presented for the pMMR population and all-comers. Treatment-related AEs occurred in 411/420 (97.9%) vs 398/411 (96.8%) treated pts in the LEN/PEMBRO vs chemo groups.Table: 39MOpMMRAll-comersLEN/PEMBRO n = 320Chemo n = 322LEN/PEMBRO n = 420Chemo n = 422OS HR (95% CI)1.02 (0.83–1.26)a0.93 (0.77–1.12)PFS HR (95% CI)0.99 (0.82–1.21)0.91 (0.76–1.09)ORR (95% CI), %50.6 (45.0–56.2)54.7 (49.0–60.2)55.7 (50.8–60.5)55.5 (50.6–60.3)Median DOR (range), mo16.1 (1.0+ to 48.7+)10.6 (1.1+ to 43.8+)23.2 (1.0+ to 49.0+)10.9 (1.1+ to 46.9+)a1-sided NI P = 0.2459875 (nonsignificant), not crossing prespecified OS NI boundary, P = 0.0158890, so no further statistical testing of efficacy endpoints was performed per prespecified multiplicity strategy for type 1 error control. Open table in a new tab a1-sided NI P = 0.2459875 (nonsignificant), not crossing prespecified OS NI boundary, P = 0.0158890, so no further statistical testing of efficacy endpoints was performed per prespecified multiplicity strategy for type 1 error control. The prespecified statistical criteria for OS and PFS in pts with pMMR IL advanced/recurrent EC were not met. Subgroup analyses identifying pts who may benefit most from LEN/PEMBRO will be presented. The safety profile was manageable and consistent with prior experience.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.011 | 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".