Pembrolizumab (pembro) vs placebo (pbo) in patients (pts) with advanced hepatocellular carcinoma (aHCC) previously treated with sorafenib: Updated data from the randomized, phase III KEYNOTE-240 study.
Notice bibliographique
Résumé
268 Background: KEYNOTE-240 (NCT02702401) examined the anti-PD-1 antibody pembro and demonstrated improvement in OS and PFS vs pbo in pts with aHCC previously treated with sorafenib. However, the study did not meet prespecified statistical significance criteria for OS and PFS. Median OS (final analysis) was 13.9 mo for pembro vs 10.6 mo for pbo (HR 0.781; 95% CI 0.611-0.998). At the first interim analysis when PFS and ORR were prespecified to be tested, median PFS was 3.0 mo for pembro vs 2.8 mo for pbo (HR 0.775; 95% CI 0.609-0.987) and ORR was 16.9% (CR, n = 3) for pembro and 2.2% (CR, n = 0) for pbo. AEs were consistent with the known safety profile of pembro. Longer-term data from KEYNOTE-240 after ~1.5 years of additional follow-up are reported. Methods: Adults with confirmed aHCC who experienced failure (progression or intolerance) to sorafenib therapy were randomized 2:1 to pembro 200 mg IV Q3W + best supportive care (BSC) or pbo + BSC for ≤35 cycles or until confirmed progression/unacceptable toxicity, pt withdrawal of consent, or investigator decision. Dual primary end points were OS and PFS, assessed by blinded independent central review (BICR) per RECIST v1.1. Secondary end points included ORR, DOR, DCR, TTP (all assessed by BICR per RECIST v1.1), and safety. Results: Of 413 pts, 278 were randomized to pembro and 135 to pbo. As of July 13, 2020, median time from randomization to data cutoff was 39.6 mo (range 31.7-48.8) for pembro and 39.8 mo (31.7-47.8) for pbo. Median OS was 13.9 mo (95% CI 11.6-16.0) for pembro and 10.6 mo (8.3-13.5) for pbo (HR 0.771; 95% CI 0.617-0.964). Estimated OS rates at 24 and 36 mo for pembro and pbo were 28.8% and 20.4% and 17.7% and 11.7%, respectively. Median PFS was 3.3 mo (95% CI 2.8-4.1) for pembro and 2.8 mo (1.6-3.0) for pbo (HR 0.703; 95% CI 0.559-0.885). Estimated PFS rate at 24 mo was 11.8% for pembro and 4.8% for pbo. ORR was 18.3% (95% CI 14.0-23.4) for pembro and 4.4% (1.6-9.4) for pbo. Median time to response was 2.7 mo (95% CI 1.2-16.9) for pembro and 2.9 mo (1.1-6.9) for pbo. Median DOR was 13.9 mo (range 1.5+ to 41.9+) for pembro and 15.2 mo (2.8-21.9) for pbo; 45.1% of responders in pembro arm and 33.3% of responders in pbo arm had DOR ≥12 mo. DCR was 61.9% for pembro and 53.3% for pbo. Best overall responses were 10 CR, 41 PR, 121 SD, and 85 PD for pembro and 0 CR, 6 PR, 66 SD, and 54 PD for pbo. The median TTP was 4.0 mo (95% CI 2.8-5.3) for pembro and 2.8 mo (1.6-3.0) for pbo. No new or unexpected AEs occurred. The frequency of sponsor-assessed immune-mediated hepatitis events did not increase with additional follow-up. There continued to be no HBV or HCV viral flare events. Conclusions: In previously treated pts with aHCC, improvement in OS and PFS was maintained over time with pembro vs pbo, and the safety profile remained consistent over time. These data support the benefit:risk profile of pembro. Clinical trial information: NCT02702401.
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 | 0,002 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».