Abstract PS12-08: MORPHEUS Hormone Receptor-Positive Breast Cancer: interim analysis of a Phase Ib/II, study of fulvestrant ± atezolizumab and abemaciclib triplet treatment in patients metastatic disease
Notice bibliographique
Résumé
Abstract BACKGROUND Endocrine therapy (ET) is the mainstay of treatment for metastatic hormone receptor-positive breast cancer (HR+ BC). ET resistance and disease progression are expected, thus novel therapies, like cancer immunotherapy, are needed. Prior data suggest that abemaciclib (abema), a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, has immunomodulatory activity. In the MORPHEUS HR+ BC study (NCT03280563), atezolizumab (atezo; anti–programmed death-ligand 1 [PD-L1]) was tested in combination with fulvestrant (FUL), with and without abema, in patients (pts) with HR+ metastatic BC. We present 24-week interim analyses. METHODS Pts with measurable disease progression during first- or second-line therapy for metastatic or inoperable locally advanced HR+ BC and prior treatment with a CDK4/6 inhibitor were randomized to receive FUL (control) or FUL + atezo (1200 mg intravenous every 3 weeks) or FUL + atezo + abema (150 mg twice a day); prior FUL was not permitted. Pts were treated until loss of clinical benefit or unacceptable toxicity. Primary endpoints were objective response rate (ORR) per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 and safety. Progression-free survival (PFS) was a secondary endpoint. Baseline tumor samples were analyzed for PD-L1 expression (SP263), CD8 T cell infiltration, and gene expression by RNAseq. RESULTS As of Dec 2022, 40, 31, and 25 pts (38, 30, and 20 evaluable pts) were randomized to atezo + abema + FUL, atezo + FUL, and FUL, respectively. Pts were followed for ≥ 24 weeks. Demographics were similar among the groups, with most pts receiving prior palbociclib (palbo) as part of their only prior metastatic therapy. Details and best confirmed ORRs are shown in the table. Median PFS was 6.34 months (95% confidence interval [CI] 5.52, 16.03) in the atezo + abema + FUL arm, 3.15 months (95% CI 1.51, 7.79) in the atezo + FUL arm, and 1.95 months (95% CI 1.45, 4.93) in the FUL arm. The hazard ratio of atezo + abema + FUL vs FUL was 0.43 (95% CI 0.24, 0.78). Safety data are shown in the table. Mild/moderate (grade 1/2) interstitial lung disease (ILD)/pneumonitis (7.7%) was observed in the atezo + abema + FUL arm. At baseline, tumors exhibited low prevalence of PD-L1 (median immune cells: 0.5%, tumor cells: 0%) and CD8 infiltration (12% inflamed phenotype), which did not associate with response in any arm. RNAseq analysis indicated that response to atezo + abema + FUL was strongly associated with low baseline expression levels of proliferation and metabolism signatures and trended with high expression of some immune signatures. CONCLUSIONS The triplet therapy of atezo + abema + FUL showed improved ORR and PFS compared with FUL monotherapy in the second- or third-line setting post-CDK4/6 inhibitor. This combination of atezo + abema + FUL was tolerable, with no unexpected safety signals, including no high-grade ILD/pneumonitis. Efficacy and safety Data are number of patients (%), unless otherwise specified. * Patient was treated in the second line and incorrectly included in this group. Abema, abemaciclib; AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; atezo, atezolizumab; CDK4/6, cyclin-dependent kinase 4/6; CI, confidence interval; ful, fulvestrant; irAE, immune-related adverse event; L, line; ORR, objective response rate; PFS, progression-free survival; TRAE, treatment-related adverse event. Citation Format: Kyung Hae Jung, Seock-Ah Im, Denise Yardley, Sara Hurvitz, Keun Seok Lee, Amir Sonnenblick, Shlomit Shachar, Antoinette Tan, Elizabeth Comen, Einav Gal-Yam, Adam Brufsky, Hope Rugo, Jing Zhu, Kelly DuPree, Vanessa Breton, Fiona Young, Richard Schwab, Edward Cha, Melinda Telli. MORPHEUS Hormone Receptor-Positive Breast Cancer: interim analysis of a Phase Ib/II, study of fulvestrant ± atezolizumab and abemaciclib triplet treatment in patients metastatic disease [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 PS12-08.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,002 |
| 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 | 0,000 |
| 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 tête enseignante, 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 ».