Abstract GS01-05: Pembrolizumab + Olaparib vs Pembrolizumab + Chemotherapy After Induction With Pembrolizumab + Chemotherapy for Locally Recurrent Inoperable or Metastatic TNBC: Randomized Open-Label Phase 2 KEYLYNK-009 Study
Notice bibliographique
Résumé
Abstract Background: Pembrolizumab (pembro) plus chemotherapy (chemo) showed statistically significant improvements in PFS and OS vs placebo + chemo in patients (pts) with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) whose tumors expressed PD-L1 with a combined positive score (CPS) ≥10 in the phase 3 KEYNOTE-355 study. Tolerable and effective maintenance regimens after induction therapy are needed to sustain clinical benefit. The PARP inhibitor olaparib is an established maintenance therapy for multiple platinum-sensitive tumor types and prior data suggest that PARP inhibitors combined with PD-1/PD-L1 inhibitors could provide an improved therapeutic effect. KEYLYNK-009 (NCT04191135) is a randomized open-label phase 2 study to evaluate the efficacy and safety of maintenance pembro + olaparib vs pembro + chemo in pts with locally recurrent inoperable or metastatic TNBC who had clinical benefit from induction with 1L pembro + platinum-based chemo. Methods: Eligible pts with measurable, locally recurrent inoperable or metastatic TNBC that had not been previously treated with chemo in the metastatic setting received induction therapy for up to 6 cycles of pembro 200 mg + chemo (carboplatin AUC 2 + gemcitabine 1000 mg/m2 on days 1 and 8) every 3 wk (Q3W). Pts with complete response (CR), partial response (PR), or stable disease (SD) after 4-6 treatment cycles were randomized 1:1 to receive pembro 200 mg Q3W + olaparib 300 mg twice daily or pembro + chemo (continued induction regimen). Olaparib or chemo was continued until progression or unacceptable toxicity; pembro was continued for up to 35 cycles (including induction treatment), progression, or unacceptable toxicity. Pts were stratified by induction response (CR or PR vs SD, by RECIST v1.1), tumor PD-L1 status (CPS ≥1 vs CPS < 1), and tumor genomic status (tBRCAm vs tBRCAwt). Dual primary endpoints were PFS per RECIST v1.1 by BICR and OS from randomization in all pts. Secondary endpoints included PFS and OS from randomization in pts with PD-L1 CPS ≥10 tumors and in pts with tBRCAm, and safety. Results: Of the 460 pts who received induction therapy, 271 were randomly assigned to pembro + olaparib (n=135) or pembro + chemo (n=136). At the Dec 15, 2022 data cutoff, median follow-up was 17.2 mo. Maintenance pembro + olaparib did not significantly improve PFS or OS vs pembro + chemo after induction therapy (Table). Median PFS was longer with pembro + olaparib vs pembro + chemo in pts with tBRCAm, but not in pts with PD-L1 CPS ≥10 tumors; a similar trend was observed for OS (Table). In 268 treated pts, treatment-related AEs (TRAEs) occurred in 114 of 135 pts (84.4%) for pembro + olaparib and in 128 of 133 pts (96.2%) for pembro + chemo. Grade ≥3 TRAEs occurred in 44 pts (32.6%) for pembro + olaparib (0 deaths) and in 91 pts (68.4%) for pembro + chemo (2 [1.5%] deaths), with 12 (8.9%) vs 26 (19.5%) discontinuations for TRAEs, respectively. Conclusions: The primary endpoints of PFS and OS were not met in an unselected population of pts with advanced TNBC. However, directionally favorable improvements in PFS and OS were observed in pts with tBRCAm with pembro + olaparib vs pembro + chemo, representing a potential maintenance strategy. Further data are required to confirm this effect. No new safety signals were observed, and there were fewer TRAEs in the pembro + olaparib group vs the pembro + chemo group. PFS and OS were evaluated from the time of randomization. *Based on stratified Cox regression model with Efron’s method of tie-handling with treatment as a covariate. NR = not reached. Citation Format: Hope Rugo, Mark Robson, Seock-Ah Im, Florence Dalenc, Eduardo Yañez Ruiz, Young-Hyuck Im, Sergii Kulyk, Oleksandr Dudnichenko, Néstor Llinás-Quintero, Shigehira Saji, Yasuo Miyoshi, Nadia Harbeck, Li Fan, Jaime Mejia, Vassiliki Karantza, David Cescon. Pembrolizumab + Olaparib vs Pembrolizumab + Chemotherapy After Induction With Pembrolizumab + Chemotherapy for Locally Recurrent Inoperable or Metastatic TNBC: Randomized Open-Label Phase 2 KEYLYNK-009 Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS01-05.
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 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| 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 | 0,002 | 0,004 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,011 | 0,002 |
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 ».