Pembrolizumab (pembro) plus enzalutamide (enza) in patients (pts) with abiraterone acetate (abi)-pretreated metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 cohort C efficacy, safety, and biomarker results.
Notice bibliographique
Résumé
5545 Background: Pembro + enza (cohort C) has shown antitumor activity and acceptable safety in abi-pretreated pts with mCRPC in the phase I/II KEYNOTE-365 study (NCT02861573). Updated results with new biomarker data from cohort C are reported. Methods: Pts who became intolerant to or for whom ≥4 weeks of abi failed in the prechemotherapy mCRPC state and who progressed within 6 mo of screening were enrolled. Pts received pembro 200 mg IV Q3W + enza 160 mg/day orally. Primary end points were PSA response rate (PSA decrease ≥50%; confirmed by a second value ≥3 weeks later), ORR per RECIST v1.1 by blinded independent central review, and safety. Key secondary end points were DCR per RECIST v1.1 (CR+PR+SD or non-CR/non-PD ≥6 mo), DOR per RECIST v1.1, radiographic PFS (rPFS) per PCWG-modified RECIST v1.1, and OS. Biospecimens (eg, blood, tissue) were collected at baseline and during the study for biomarker analysis, including tissue PD-L1 expression, androgen receptor variant 7 (AR-v7) expression in circulating tumor cells (CTCs), and a T-cell-inflamed gene expression profile (GEP). Results: Of 103 enrolled pts, 102 were treated; 39% of treated pts had measurable disease. Median (range) time from enrollment to data cutoff was 19.1 mo (1.1-28.8) for all pts and 21.4 mo (15.1-28.8) for pts with ≥27 wks’ follow-up (n=69). Confirmed PSA response rate was 22% in 101 pts with a baseline PSA assessment. Median time to PSA progression was 3.5 mo (95% CI, 2.9-4.0). In pts with measurable disease and ≥27 wks’ follow-up (n=25), confirmed ORR was 12% (2 CRs, 1 PR) and DCR was 32%. Median DOR was not reached (range, 0.0+ to 24.4+ mo); 2 pts had a response for ≥6 mo. In all pts, median (95% CI) rPFS was 6.1 mo (4.4-6.5) and median OS was 20.4 mo (15.5-NR). At 6 mo, rPFS rate was 55.1% and OS rate was 88.2%. Treatment-related AEs occurred in 92 pts (90%); most frequent (≥20%) were fatigue (38%), nausea (22%), and rash (20%). Grade 3-5 treatment-related AEs occurred in 40 pts (39%). Three pts died of AEs (1 AE was treatment related [cause unknown]). Of all pts, 29% had PD-L1+ tumors (combined positive score ≥1). Of 51 pts with AR-v7 data, 13.7% were AR-v7+ and 86.3% were AR-v7−. GEP was not significantly associated with ORR or PSA response. Conclusions: Pembro + enza continued to show activity in pts with abi-pretreated mCRPC. Safety of the combination was consistent with the known profiles of pembro and enza. A phase III study of this combination is ongoing (KEYNOTE-641, NCT03834493). Clinical trial information: NCT02861573 .
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».