CDK4/6 Inhibition With Abemaciclib in Patients With Previously Treated Advanced Renal Cell Carcinoma

被引:0
作者
Mcgregor, Bradley A. [1 ]
Xie, Wanling [1 ]
Berg, Stephanie A. [1 ]
Xu, Wenxin [1 ]
Viswanathan, Srinivas R. [1 ]
Mcdermott, David [2 ]
Signoretti, Sabina [3 ]
Kaelin, William G. [1 ]
Choueiri, Toni K. [1 ]
机构
[1] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA
[2] Beth Israel Deaconess Med Ctr, Boston, MA USA
[3] Brigham & Womens Hosp, Boston, MA USA
关键词
CDK4/6; inhibitiors; HF2; inhibitors; Phase 1b clinical trial; Safety; Clear cell renal cell carcinoma;
D O I
10.1016/j.clgc.2025.102318
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
This single arm phase 1b study exploring safety and efficacy of abemaciclib in pretreated RCC with a clear cell component to our knowledge is the first to report activity of CDK4/6 inhibition monotherapy in advanced RCC. No responses were seen in 11 patients with no new toxicity signals. While no activity as a monotherapy, ongoing trials exploring CDK4/6 inhibitors in combination with active therapeutic agents must continue, before we rule out this class of agents in this disease setting a. Background: Preclincal data provide a rationale for cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors alone and in combination with HIF-2 alpha inhibitors in treatment of clear cell renal cell carcinoma (ccRCC), with randomized phase 2 clinical trials currently open exploring the combination of palbociclib with belzutifan vs belzutifan in treatment resistant ccRCC (NCT05468697). However, single agent activity for CDK4/6 inhibitors in ccRCC has not been reported. In this multi-center phase 1b clinical trial ( NCT04627064 ), we investigated the safety and efficacy of monotherapy with abemaciclib, an oral CDK4/6 inhibitor in patients with advanced pretreated RCC. Methods: Adult patients with advanced RCC with a clear cell component and ECOG status of <= 2 progressing after at least 1 prior regimen including immunotherapy and a VEGFR TKI received abemaciclib 200 mg twice daily in 4-week cycles until progression or unacceptable toxicity. The primary objective was to evaluate the objective response rate (ORR) of abemaciclib with a secondary endpoint of safety. First imaging was performed after 8 weeks or 2 cycles. Response was assessed per RECIST 1.1 and toxicity graded per CTCAE v5.0. Results: Eleven patients were enrolled between December 31, 2020 and October 03, 2023. Median age was 62 years (range 54-68); 73% ( n = 8) had IMDC intermediate risk disease and 1 patient had translocation RCC with a clear cell component. Median number of prior therapies was 4 (range 1-9). ORR was 0% (0/11; 8 progressive disease, 1 stable disease stopping for clinical progression, 2 not evaluable with clinical progression). About 27% ( n = 3) experienced grade >= 3 treatment-related adverse events (diarrhea n = 1, nausea n = 1, neutropenia n = 1). Conclusion: In patients with heavily pretreated metastatic RCC, abemaciclib monotherapy had no clinically meaningful activity without new toxicity signals. This data will offer important insight into interpretation of results for ongoing trials exploring CDK4/6 inhibition in combination with HIF-2 alpha inhibitors and immunotherapy.
引用
收藏
页数:5
相关论文
共 50 条
  • [31] Abemaciclib: The First FDA-Approved CDK4/6 Inhibitor for the Adjuvant Treatment of HR+HER2-Early Breast Cancer
    Raheem, Farah
    Ofori, Henry
    Simpson, Lacey
    Shah, Vishal
    ANNALS OF PHARMACOTHERAPY, 2022, 56 (11) : 1258 - 1266
  • [32] Evaluation of CDK4/6 inhibitors in first-line in symptomatic and asymptomatic patients with metastatic breast cancer
    Oner, Irem
    Turkel, Alper
    Anik, Hicran
    Arslan, Ulku Yalcintas
    Karacin, Cengiz
    FUTURE ONCOLOGY, 2024, : 3443 - 3450
  • [33] Potential biomarkers of CDK4/6 inhibitors in hormone receptor-positive advanced breast cancer
    Fang, Hehui
    Huang, Doudou
    Yang, Fang
    Guan, Xiaoxiang
    BREAST CANCER RESEARCH AND TREATMENT, 2018, 168 (02) : CP8 - 297
  • [34] Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma
    Ye, Dingwei
    Liu, Jiyan
    Zhou, Aiping
    Zou, Qing
    Li, Hanzhong
    Fu, Cheng
    Hu, Hailong
    Huang, Jian
    Zhu, Shaoxing
    Jin, Jie
    Ma, Lulin
    Guo, Jianming
    Xiao, Jun
    Park, Se Hoon
    Zhang, Dahong
    Qiu, Xiusong
    Bao, Yuanyuan
    Zhang, Lilin
    Shen, Wei
    Bi, Feng
    CANCER SCIENCE, 2021, 112 (01) : 305 - 313
  • [35] Steatotic liver disease in metastatic breast cancer treated with endocrine therapy and CDK4/6 inhibitor
    Malon, Diego
    Molto, Consolacion
    Prasla, Shopnil
    Cuthbert, Danielle
    Pathak, Neha
    Berner-Wygoda, Yael
    Di Lorio, Massimo
    Li, Meredith
    Savill, Jacqueline
    Mittal, Abhenil
    Amir, Eitan
    Jhaveri, Kartik
    Nadler, Michelle B.
    BREAST CANCER RESEARCH AND TREATMENT, 2025, 210 (02) : 405 - 416
  • [36] CDK4/6 Inhibition Enhances the Efficacy of Standard Chemotherapy Treatment in Malignant Pleural Mesothelioma Cells
    Terenziani, Rita
    Galetti, Maricla
    La Monica, Silvia
    Fumarola, Claudia
    Zoppi, Silvia
    Alfieri, Roberta
    Digiacomo, Graziana
    Cavazzoni, Andrea
    Cavallo, Delia
    Corradi, Massimo
    Tiseo, Marcello
    Petronini, Pier Giorgio
    Bonelli, Mara
    CANCERS, 2022, 14 (23)
  • [37] Comparison of healthcare resource utilization and costs of patients with HR+/HER2-advanced breast cancer treated with ribociclib versus other CDK4/6 inhibitors
    Burne, Rebecca
    Balu, Sanjeev
    Guerin, Annie
    Bungay, Rebecca
    Sin, Roxana
    Paul, Mary Lisha
    JOURNAL OF MEDICAL ECONOMICS, 2021, 24 (01) : 806 - 815
  • [38] Discovery of a novel CDK4/6 and HDAC dual-targeting agent for the treatment of hepatocellular carcinoma
    Niu, Zizhou
    Shi, Zhichao
    Wu, Guoxiang
    Liu, Yanping
    Xie, Weibin
    Liu, Fakai
    Fan, Tingting
    Shu, Kaifei
    Huang, Qiuhua
    Dai, Mengmeng
    Zhi, Cailian
    Qiu, Cheng
    Li, Yilin
    Wu, Lihong
    Liu, Funian
    Zhang, Yijie
    Wu, Tingbiao
    Chen, Yan
    Liu, Zijian
    Hao, Yue
    Jiang, Yuyang
    BIOORGANIC CHEMISTRY, 2025, 154
  • [39] Do CDK4/6 inhibitors have potential as targeted therapeutics for squamous cell cancers?
    Kalu, Nene N.
    Johnson, Faye M.
    EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2017, 26 (02) : 207 - 217
  • [40] CDK4/6 inhibitor plus endocrine therapy for advanced breast cancer: results from a web-based survey in Japan
    Nakayama, Takahiro
    Xu, Linghua
    Muramatsu, Yasuaki
    FUTURE ONCOLOGY, 2025, 21 (03) : 321 - 330