CDK4/6抑制剂活性及影响老年亚组患者生存的参数:土耳其肿瘤学组(TOG)回顾性研究

Activity of CDK4/6 inhibitors and parameters affecting survival in elderly patients in age-subgroups: Turkish Oncology Group (TOG) retrospective study.

作者信息

Kahraman Seda, Hizal Mutlu, Demirel Burcin Cakan, Guven Deniz Can, Gumusay Ozge, Uluc Basak Oyan, Bayram Ertugrul, Gulbagci Burcu, Yasar Alper, Davarci Sena Ece, Mocan Eda Eylemer, Acar Omer, Isik Deniz, Aydin Esra, Karakas Yusuf, Ozcelik Melike, Keser Murat, Okutur Sadi Kerem, Eren Onder, Menekse Serkan, Aydin Dincer, Yilmaz Funda, Dogan Ozlem, Ozkanli Gulhan, Yucel Hakan, Sunar Veli, Aykan Musa Baris, Ozdemir Ozlem, Duman Berna Bozkurt, Keskinkilic Merve, Sakalar Teoman, Inal Ali, Karaoglanoglu Muge, Aksoy Asude, Er Muhammed Muhiddin, Turhal Nazim Serdar, Kalkan Nurhan Onal, Sendur Mehmet Ali Nahit

机构信息

Ankara Bilkent City Hospital, Department Of Medical Oncology, Ankara Yildirim Beyazit University, Ankara, 06800, Turkey.

Department Of Medical Oncology, Pamukkale University Hospital, Denizli, Turkey.

出版信息

BMC Cancer. 2024 Dec 30;24(1):1592. doi: 10.1186/s12885-024-13357-5.

Abstract

Highly selective inhibitors of cyclin-dependent kinase 4 and 6 (CDK4/6is) have emerged as a standart of care for first- and second-line therapies in combination with endocrine therapy (ET) for HR+/HER2- metastatic breast cancer (MBC) patients. It has been reported that combination therapy is more effective than ET alone and is safe in elderly patients as well as young patients. Nevertheless, elderly and very old patients with HR+/HER2-MBC treated with CDK4/6 inhibitor (CDK4/6i) combinations are relatively underrepresented in randomized controlled trials. To contribute to the literature, we investigated the real-world efficacy, factors associated with survival and the rates of adverse events (AEs) of the treatment with palbociclib or ribociclib plus ET in the HR+/HER2- MBC patient cohort over the age of 65 for age subgroups. In this retrospective study, 348 patients were divided into subgroups: 65-69 years old, 70-79 years old and 80 years and older. Median PFS (mPFS) for whole group was 18.3 (95% CI,14.3-22.3) months. There was no significant difference in mPFS between age groups (p = 0.75). The estimated median OS (mOS) was 39.5 (95% CI, 24.9-54.1) months and there was no significant difference between age groups (p = 0.15). There was a meaningfull numerical difference that did not reach statistical significance in patients who received CDK4/6i treatment as the first line for MBC. Grade 3-4 AEs were reported in 42.7% for the entire group, and neutropenia was the most common (37.3%). It can be concluded that combination therapy with palbociclib or ribociclib with an ET partner has similar efficacy and is safe among subgroups of older patients diagnosed with HR+/HER2-MBC.

摘要

细胞周期蛋白依赖性激酶4和6的高选择性抑制剂(CDK4/6抑制剂)已成为激素受体阳性/人表皮生长因子受体2阴性(HR+/HER2-)转移性乳腺癌(MBC)患者一线和二线治疗联合内分泌治疗(ET)的标准治疗方案。据报道,联合治疗比单纯内分泌治疗更有效,且在老年患者和年轻患者中均安全。然而,在随机对照试验中,接受CDK4/6抑制剂(CDK4/6i)联合治疗的HR+/HER2-MBC老年和高龄患者的比例相对较低。为丰富相关文献,我们调查了年龄在65岁以上的HR+/HER2-MBC患者队列中,使用哌柏西利或瑞博西利联合ET治疗的真实疗效、与生存相关的因素以及不良事件(AE)发生率。在这项回顾性研究中,348例患者被分为几个亚组:65-69岁、70-79岁和80岁及以上。全组的中位无进展生存期(mPFS)为18.3(95%CI,14.3-22.3)个月。各年龄组之间的mPFS无显著差异(p = 0.75)。估计的中位总生存期(mOS)为39.5(95%CI,24.9-54.1)个月,各年龄组之间无显著差异(p = 0.15)。在将CDK4/6i治疗作为MBC一线治疗的患者中,存在有意义的数值差异,但未达到统计学显著性。全组报告的3-4级AE为42.7%,中性粒细胞减少最为常见(37.3%)。可以得出结论,哌柏西利或瑞博西利与ET联合治疗在诊断为HR+/HER2-MBC的老年患者亚组中具有相似的疗效且安全。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97c/11687141/a0c63f2675b9/12885_2024_13357_Fig1_HTML.jpg

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