Pembrolizumab (pembro) plus dabrafenib (dab) and trametinib (tram) in <i>BRAF</i><sup>V600E/K</sup>-mutant melanoma: Long-term follow-up of KEYNOTE-022 parts 1, 2, and 3.
Notice bibliographique
Résumé
9516 Background: KEYNOTE-022 (NCT02130466) was a phase 1/2 study of pembro + dab + tram or pembro + tram in patients (pts) with unresectable stage III/IV melanoma (parts 1-3) or solid tumors (parts 4 and 5). In previous analyses of pts with BRAFV600E/K -mutant melanoma, pembro + dab + tram was shown to have manageable safety in parts 1-3, albeit with a higher incidence of TRAEs in part 3, and substantially improved PFS, DOR, and OS vs placebo + dab + tram in part 3, although the primary end point of a statistically significant improvement in PFS was not met. Long-term follow-up of pts with BRAFV600E/K-mutant melanoma in parts 1-3 are presented. Methods: Eligible pts were ≥18 y with unresectable stage III/IV BRAFV600E/K-mutant melanoma, ≥1 measurable lesion per RECIST v1.1, ECOG PS 0/1, and no prior systemic therapy for advanced disease. In parts 1 and 2, which involved dose finding and confirmation, pts received pembro 2 mg/kg IV Q3W + dab 150 mg PO BID + tram 2 mg PO QD (MTD). In part 3, pts were randomized 1:1 to pembro + dab + tram at MTD or placebo + dab + tram. Primary end points were safety, tolerability, and MTD (parts 1 and 2); ORR per RECIST v1.1 by investigator review (part 2); and PFS per RECIST v1.1 by investigator review (part 3). Data cutoff was July 14, 2021. Results: Median (range) study follow-up was 72.9 mo (68.4-84.5) in parts 1 and 2 (n = 15) and 61.2 mo (50.7-67.5) for all pts (n = 120; 60 each arm) in part 3. Safety of pembro + dab + tram in parts 1 and 2 was consistent with prior reports; grade 3/4 TRAEs occurred in 11 pts (73%), and no additional DLTs occurred. ORR in parts 1 and 2 was 67% (95% CI, 38-88), which was similar to that reported at an earlier data cut (73% [95% CI, 45-92]); median DOR was 19.4 mo (95% CI, 2.8-NR), median OS was NR (95% CI, 10.3-NR), 48-mo OS rate was 60%, median PFS was 15.2 mo (95% CI, 4.2-NR), and 48-mo PFS rate was 28% (Ribas A et al. Nat Med. 2019;25:936-940). In part 3, median PFS was 17.0 mo (95% CI, 11.3-NR) for pembro + dab + tram vs 9.9 mo (95% CI, 6.7-15.6) for placebo + dab + tram (HR, 0.46; 95% CI, 0.29-0.74) and 24-mo PFS rate was 47% vs 16%, and median OS was 46.3 mo (95% CI, 23.9-NR) vs 26.3 mo (95% CI, 18.2-38.6); and 24-mo OS rate was 63% vs 52%, respectively. ORR was 65% (95% CI, 52-77) for pembro + dab + tram vs 72% (95% CI, 59-83) for placebo + dab + tram; median DOR was 30.2 mo (95% CI, 14.1-NR) vs 12.1 mo (95% CI, 6.0-15.7). Safety in part 3 was similar to prior reports; grade 3-5 TRAEs occurred in 42 pts (70%) in the pembro + dab + tram arm vs 27 pts (45%) in the placebo + dab + tram arm (Ferrucci PF et al. J Immunother Cancer. 2020;8:e001806). No additional grade 5 TRAEs occurred (1 grade 5 pneumonitis had occurred at prior analysis). Conclusions: At long-term follow-up, first-line pembro + dab + tram continued to show improved PFS, DOR, and OS compared with placebo + dab + tram in pts with BRAFV600E/K-mutant melanoma. TRAEs were more common with pembro + dab + tram but no new safety signals were identified. Clinical trial information: NCT02130466.
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 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
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 ».