Re-VOLVE: Phase II clinical trial in women with ovarian cancer progressing post-PARP inhibitor with treatment adapted to real-time assessment of evolving genomic resistance.
Notice bibliographique
Résumé
5561 Background: As the use of PARPi increases in high-grade serous ovarian cancer (HGSOC) resistance mechanisms ultimately arise. Emerging therapeutic strategies to overcome PARPi resistance is a pressing concern. Re-VOLVE study is a phase II in HGSOC women post-PARPi with treatment adapted to real-time assessment of evolving genomic resistance to guide treatment decision (NCT05065021). Methods: It enrolled patients (pts) with HGSOC progressing post-PARPi to receive induction phase (IP) 2-3 cycles of niraparib 200-300mg/bevacizumab 7.5mg/kg followed by personalized phase based on initial RECIST response and real-time assessment of evolving genomic resistance from baseline biopsy (whole genome RNA sequencing/WGTS) and ctDNA (12 gene panel). If progression/stable disease after IP pts were assigned to cohort A (niraparib/bevacizumab/dostarlimab 500mg) if no resistance mechanisms and to B (weekly paclitaxel 80mg/m2/bevacizumab/dostarlimab) if any present and to cohort C (continue niraparib/bevacizumab) if partial response after IP. Primary endpoint was to assess response rate of combination therapies. Results: 50 pts were screened; 7 were screen fail and 43 were enrolled. Of the 43, 3 pts were taken off due to progression during IP, 1 withdrew from study, 3 are on IP and 36 continued to personalized phase. Of these 36, 78% were white, 20% Asian, 2% others; 69% BRCA wild-type (25/36); 61% platinum-resistant (PR;22/36) and 39% platinum-sensitive (PS;14/36). Median age 62.5 years (33-87). Pts had median 2 prior therapy lines (1-5); 22% (8/36) prior bevacizumab. Median days from collection to ctDNA results were 59 days and to WGTS 54 days. Twenty-seven pts (75%) had biopsy and ctDNA to guide therapy. 36 pts were assigned to personalized phase: 78% cohort A, 14% to B (4 CCNE1 amplification and 1 CHEK2 mutation) and 8% to C (3 with response during IP). Of the 31/36 pts assessed for response during personalized phase (others too early) 10 achieved partial response (32.2%; 7 PR, 3 PS). Nineteen pts (61.3%; 11 PR, 8 PS) had stable disease. By cohort, 3 pts had partial response (12.5%; 3/24) cohort A, 4 partial response cohort B (100%; 4/4 all with resistance mechanisms) and 3 partial response (100%; 3/3) cohort C. Median PFS in the personalized phase was 7.8 months (m) for those in cohort A, 6.2m for B and 13.1m for C. Median PFS for PR pts was 6.9m (4.4-13.1) and for PS pts not reached. Grade (G) 3 AE related to therapy per cohort: A) 4 pts with anemia, 2 neutropenia, 1 thrombocytopenia, 1 nausea; B) 2 pts neutropenia; C) no G3. No G4 AE. No G3-G4 immune related AE. Conclusions: These findings highlight the potential clinical activity of a chemo-free approach and confirmed the feasibility of guiding personalized therapy in real-time in recurrent OC pts post-PARPi. This strategy was safe and provided clinical benefit to some pts. Further translational analysis is ongoing. Clinical trial information: NCT05065021 .
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) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 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 ».