A phase II study of fulvestrant plus abemaciclib in hormone receptor–positive advanced or recurrent endometrial cancer Journal Article


Authors: Green, A. K.; Zhou, Q.; Iasonos, A.; Zammarrelli, W. A. 3rd; Weigelt, B.; Ellenson, L. H.; Chhetri-Long, R.; Shah, P.; Loh, J.; Hom, V.; Selenica, P.; Erinjeri, J.; Petkovska, I.; Chandarlapaty, S.; Cohen, S.; Grisham, R.; Konner, J.; Rubinstein, M. M.; Tew, W.; Troso-Sandoval, T.; Aghajanian, C.; Makker, V.
Article Title: A phase II study of fulvestrant plus abemaciclib in hormone receptor–positive advanced or recurrent endometrial cancer
Abstract: Purpose: Inhibition of the cyclin D–cyclin-dependent kinase (CDK)4/6–INK4–retinoblastoma pathway can overcome acquired or de novo treatment resistance to endocrine monotherapy. Responses to endocrine monotherapy in advanced endometrial cancer are suboptimal, perhaps due to genomic alterations that promote estrogen receptor–independent cyclin D1–CDK4/6 activation. We hypothesized that the addition of abemaciclib, a CDK4/6 kinase inhibitor, to antiestrogen therapy with fulvestrant would be an effective therapeutic strategy in patients with advanced or recurrent endometrial cancer. Patients and Methods: In this phase II study, patients with advanced or recurrent endometrial cancer received 150 mg of abemaciclib orally twice daily with 500 mg of fulvestrant intramuscularly monthly with a 2-week loading dose. Eligibility included estrogen receptor or progesterone receptor expression ≥1% by IHC, measurable disease, ≤2 prior lines of chemotherapy, and ≤1 prior lines of hormonal therapy. The primary endpoint was the objective response rate by RECIST v1.1. Results: Twenty-seven patients initiated therapy, and 25 were evaluable for efficacy. Eleven patients achieved partial response; 10 responses (91%) were in copy number–low/no specific molecular profile tumors, 1 response (9%) was in a microsatellite instability–high tumor, and no responses were observed in copy number–high/ TP53abnormal tumors. The objective response rate was 44% (90% confidence interval, 27.0%–62.1%). The median duration of response was 15.6 months. The median progression-free survival was 9.0 months (90% confidence interval, 1.8–20.4). The most common grade ≥3 treatment-related adverse events were neutropenia (26%) and anemia (19%); no new safety signals were identified. Conclusions: The combination of abemaciclib and fulvestrant has promising activity with durable responses in advanced or recurrent endometrial cancer; a randomized trial is planned. See related commentary by Garg and Oza, p. 2073 ©2024 American Association for Cancer Research.
Keywords: immunohistochemistry; adult; cancer chemotherapy; controlled study; human tissue; protein expression; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; gene mutation; major clinical study; overall survival; genetics; clinical trial; fatigue; mortality; neutropenia; cancer recurrence; squamous cell carcinoma; advanced cancer; diarrhea; drug dose reduction; drug efficacy; side effect; treatment duration; paclitaxel; cancer radiotherapy; follow up; antineoplastic agent; endometrioid carcinoma; endometrial neoplasms; endometrium cancer; anorexia; metabolism; gene; carboplatin; progression free survival; phase 2 clinical trial; neoplasm recurrence, local; anemia; nausea; vomiting; antineoplastic combined chemotherapy protocols; creatinine; pathology; phosphatidylinositol 3 kinase; protein p53; histology; injection site reaction; loading drug dose; aspartate aminotransferase; hyponatremia; maculopapular rash; body mass; multicenter study; tumor recurrence; mismatch repair; adjuvant chemotherapy; microsatellite instability; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; carcinoma; open study; receptors, estrogen; receptors, progesterone; hormonal therapy; leukocyte count; estrogen receptor; progesterone receptor; drug therapy; colloid carcinoma; transitional cell carcinoma; endometrium tumor; benzimidazole derivative; benzimidazoles; lymphocyte count; antiestrogen; anaplastic carcinoma; fulvestrant; platelet count; enterocolitis; copy number variation; receptor subtype; hypertransaminasemia; exploratory research; estrogen receptor alpha; uterine papillary serous carcinoma; overall response rate; cancer prognosis; response evaluation criteria in solid tumors; ctnnb1 gene; very elderly; lenvatinib; humans; human; female; article; pembrolizumab; abemaciclib; aminopyridines; aminopyridine derivative; antigestagen; ecog performance status; cervical clear cell adenocarcinoma
Journal Title: Clinical Cancer Research
Volume: 31
Issue: 11
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2025-06-01
Start Page: 2088
End Page: 2096
Language: English
DOI: 10.1158/1078-0432.Ccr-24-1999
PUBMED: 39561275
PROVIDER: scopus
PMCID: PMC12086264
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Angela K. Green -- Source: Scopus
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MSK Authors
  1. Vicky Makker
    265 Makker
  2. Jason Konner
    156 Konner
  3. Qin Zhou
    254 Zhou
  4. Alexia Elia Iasonos
    363 Iasonos
  5. Rachel Nicole Grisham
    170 Grisham
  6. Joseph Patrick Erinjeri
    202 Erinjeri
  7. William P Tew
    245 Tew
  8. Britta Weigelt
    633 Weigelt
  9. Pier Selenica
    190 Selenica
  10. Angela Kellen Green
    42 Green
  11. Vania Hom
    4 Hom
  12. Lora Hedrick Ellenson
    109 Ellenson
  13. Seth Matthew Cohen
    21 Cohen
  14. Pooja Shah
    5 Shah
  15. Jade B. Loh
    1 Loh