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Efficacy of everolimus and letrozole with or without ribociclib in recurrent endometrial cancer: a phase 2 randomized clinical trial

Jeffrey A. How, Shannon N. Westin, Melissa Pham, Barrett Lawson, Minxing Chen, Nidhi Tandon, Ying Yuan, Rugang Zhang, Amir A. Jazaeri, Anil K. Sood, Michaela Onstad Grinsfelder, Kathleen M. Schmeler, David J. Vining, Samantha M. Fix, Yibo Dai, Mikayla B. Bowen, Karen H. Lu, Melinda S. Yates, Russell Broaddus, Pamela T. Soliman

Nature Communications · 2026

Vollständiger Abstract

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Abstract In this phase II trial, patients with endometrial cancer (EC) were randomized to everolimus/letrozole with (experimental arm) or without ribociclib (control arm) (ClinicalTrials.gov Identifier: NCT03008408). The primary endpoint was progression-free survival (PFS). Secondary endpoints included toxicity, overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). For all-comers, there was no difference in PFS (HR 0.78, 95% CI 0.4-1.4, p = 0.38), OS (HR 0.8, 95% CI 0.4-1.5, p = 0.46), ORR (44.1% vs 25.7%, p = 0.11), or toxicity-related treatment discontinuation (4 [8.6%] vs 3 [11.4%], p = 0.22). Among those with prior endocrine therapy, ORR was higher in the experimental arm (61.5% vs 0.0%, p < 0.001). Within the experimental arm, CTNNB1 mut tumors were associated with improved PFS (HR 0.27, 95% CI 0.1-0.7, p = 0.006) and OS (HR 0.24, 95% CI 0.1-0.7, p = 0.004) compared to those with non- CTNNB1 mut tumors. Despite no survival improvement in all-comers, addition of ribociclib to everolimus/letrozole may improve efficacy in patients with prior endocrine therapy and cases with CTNNB1 mut tumors may have prolonged response.

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Autor:innen
Jeffrey A. How, Shannon N. Westin, Melissa Pham, Barrett Lawson, Minxing Chen, Nidhi Tandon, Ying Yuan, Rugang Zhang, Amir A. Jazaeri, Anil K. Sood, Michaela Onstad Grinsfelder, Kathleen M. Schmeler, David J. Vining, Samantha M. Fix, Yibo Dai, Mikayla B. Bowen, Karen H. Lu, Melinda S. Yates, Russell Broaddus, Pamela T. Soliman
Quelle
Nature Communications
Publikation
2026-01-01
Band / Ausgabe
Nicht angegeben
Seiten
Nicht angegeben
ISSN / ISBN
2041-1723
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Jeffrey A. How, Shannon N. Westin, Melissa Pham, Barrett Lawson, Minxing Chen, Nidhi Tandon, Ying Yuan, Rugang Zhang, Amir A. Jazaeri, Anil K. Sood, Michaela Onstad Grinsfelder, Kathleen M. Schmeler, David J. Vining, Samantha M. Fix, Yibo Dai, Mikayla B. Bowen, Karen H. Lu, Melinda S. Yates, Russell Broaddus, Pamela T. Soliman (2026). Efficacy of everolimus and letrozole with or without ribociclib in recurrent endometrial cancer: a phase 2 randomized clinical trial. Nature Communications. https://doi.org/10.1038/s41467-026-77049-3
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