Phase II study of the efficacy and safety of palbociclib in patients with recurrent ovarian cancer.

IF 4.7 2区 医学 Q1 OBSTETRICS & GYNECOLOGY
Gottfried E Konecny, Tara M Davidson, Coriolan L Lebreton, Leah A Marsh, Deandra K Chetram, Hunter J Atkinson, Melissa C Larson, Ann L Oberg, Nabilah Abdelaal, Jordyn Silverstein, Aminah Jatoi, Anita Washburn, Jill Burton, Sean Dowdy, Liying Zhang, Dorothy Hallberg, Victor E Velculescu, Dennis J Slamon, Andrea E Wahner-Hendrickson
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引用次数: 0

Abstract

Objective: We describe a phase II clinical trial evaluating the safety and efficacy of the oral CDK4/6 inhibitor palbociclib in patients with recurrent ovarian cancer.

Methods: Eligible patients with Response Evaluation Criteria in Solid Tumors (RECIST) and/or CA-125 measurable recurrent ovarian cancer were treated with oral palbociclib 125 mg daily for 21 days of a 28-day cycle. Patients with hormone receptor-positive tumors were allowed to concurrently receive an aromatase inhibitor. The primary endpoint was the biochemical response rate, determined by CA-125 response based on Gynecologic Cancer InterGroup criteria. Genomic analyses were performed using targeted next-generation sequencing.

Results: The biochemical response rate among 40 patients was 8.3% (95% CI 2.2 to 23.6), and the objective response rate by CA-125 criteria and/or RECIST was 10.5% (95% CI 3.4 to 25.7). Median progression-free survival was 3.2 months. Progression-free survival rates at 6 and 12 months were 25% and 7.5%, respectively. Two patients diagnosed with recurrent low-grade serous ovarian cancer experienced long-term disease stabilization for more than 37 and 9 months, triggering a review of 12 additional low-grade serous ovarian cancer patients treated outside of the phase II trial. Exploratory tumor genomic profiling revealed potential predictors of sensitivity (CDKN2A deletion) or resistance (CCNE1 amplification or RB1 deletion), which require additional independent validation.

Conclusions: Palbociclib demonstrated only modest clinical activity in unselected patients with ovarian cancer. However, cyclin-dependent kinases 4/6 inhibition showed promising clinical activity in low-grade serous ovarian cancer, warranting further study in this subtype. Further biomarker analyses may facilitate patient selection in high-grade serous ovarian cancer.

帕博西尼治疗复发性卵巢癌的有效性和安全性的II期研究。
目的:我们描述了一项评估口服CDK4/6抑制剂palbociclib治疗复发性卵巢癌患者的安全性和有效性的II期临床试验。方法:符合实体瘤反应评价标准(RECIST)和/或CA-125可测量的复发性卵巢癌患者口服帕博西尼125mg,每日21天,28天为一个周期。激素受体阳性肿瘤患者被允许同时接受芳香酶抑制剂治疗。主要终点是生化反应率,由基于妇科癌症组间标准的CA-125反应确定。使用靶向下一代测序进行基因组分析。结果:40例患者的生化反应率为8.3% (95% CI 2.2至23.6),CA-125标准和/或RECIST的客观反应率为10.5% (95% CI 3.4至25.7)。中位无进展生存期为3.2个月。6个月和12个月的无进展生存率分别为25%和7.5%。两名诊断为复发性低级别浆液性卵巢癌的患者经历了超过37个月和9个月的长期疾病稳定,引发了对另外12名在II期试验之外接受治疗的低级别浆液性卵巢癌患者的审查。探索性肿瘤基因组分析揭示了敏感性(CDKN2A缺失)或耐药性(CCNE1扩增或RB1缺失)的潜在预测因子,这需要额外的独立验证。结论:帕博西尼在未选择的卵巢癌患者中仅表现出适度的临床活性。然而,周期蛋白依赖性激酶4/6抑制在低级别浆液性卵巢癌中显示出良好的临床活性,值得对该亚型进行进一步研究。进一步的生物标志物分析可能有助于高级别浆液性卵巢癌患者的选择。
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来源期刊
CiteScore
6.60
自引率
10.40%
发文量
280
审稿时长
3-6 weeks
期刊介绍: The International Journal of Gynecological Cancer, the official journal of the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology, is the primary educational and informational publication for topics relevant to detection, prevention, diagnosis, and treatment of gynecologic malignancies. IJGC emphasizes a multidisciplinary approach, and includes original research, reviews, and video articles. The audience consists of gynecologists, medical oncologists, radiation oncologists, radiologists, pathologists, and research scientists with a special interest in gynecological oncology.
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