Andrikopoulou Angeliki, Fiste Oraianthi, Liontos Michalis, Dimopoulos Meletios-Athanasios, Zagouri Flora
Department of Clinical Therapeutics, Alexandra Hospital, Medical School, 11528 Athens, Greece.
Medical School, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece.
Cancers (Basel). 2021 Jan 26;13(3):465. doi: 10.3390/cancers13030465.
Treatment with aromatase inhibitors (AIs) is fundamental in women with hormone receptor-positive breast cancer in the adjuvant as well as the metastatic setting. Even though it is considered to be a well-tolerated therapy, aromatase inhibitor-associated musculoskeletal syndrome (AIMSS) is the most common adverse event encountered by breast cancer patients. CDK4/6 inhibitors have emerged as a new treatment strategy in metastatic hormone receptor-positive breast cancer. However, the impact of CDK4/6 inhibitors on musculoskeletal symptoms caused by AIs is not well-defined.
This systematic review aims to identify the frequency of joint symptoms induced by treatment with AIs and CDK4/6 inhibitors in the metastatic setting.
Eligible articles were identified by a search of existing literature for the period 2005/01/01-2021/01/01; The algorithm consisted of a predefined combination of the following keywords "breast", "cancer", "aromatase inhibitors", "CDK4/6", "phase III".
This study was performed in accordance with PRISMA guidelines. All randomized controlled Phase III trials (RCTs) evaluating the administration of third-generation aromatase inhibitors (AIs) and CDK4/6 inhibitors in postmenopausal women in the metastatic setting were considered eligible for this review.
Overall, 16 randomized control trials (RCTs) were retrieved, of which nine studies explored the administration of AIs in the metastatic setting and seven studies investigated the combination of CDK4/6 inhibitors and AIs. Arthralgia was reported in 1-47% of patients treated with AIs and 5.8-33.3% of patients treated with CDK4/6 inhibitors. Myalgias occurred in 2-23.7% of patients receiving AIs compared with 4.8-11.9% of patients treated with CDK4/6 inhibitors. The incidence of back pain was 7-32.9% vs. 2.9-8.5% in postmenopausal women with metastatic disease treated with AIs and CDK4/6 inhibitors, respectively. Bone pain was reported in 7-32.9% of postmenopausal women treated with AIs and 2.9-8.5% of women treated with CDK4/6 inhibitors.
AI treatment-induced musculoskeletal syndrome is an adverse event affecting over one-third (20-47%) of postmenopausal patients treated with AIs that often leads to treatment discontinuation. Data from RCTs provide evidence that the incidence of musculoskeletal symptoms is relatively decreased upon CDK4/6 inhibitor administration. CDK4/6 inhibitors may provide a protective role against AIMSS development.
芳香化酶抑制剂（AIs）治疗对于激素受体阳性乳腺癌女性患者的辅助治疗及转移性疾病治疗至关重要。尽管其被认为是一种耐受性良好的疗法，但芳香化酶抑制剂相关肌肉骨骼综合征（AIMSS）却是乳腺癌患者最常遇到的不良事件。细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂已成为转移性激素受体阳性乳腺癌的一种新治疗策略。然而，CDK4/6抑制剂对AIs所致肌肉骨骼症状的影响尚不明确。
本系统评价旨在确定在转移性疾病背景下，AIs和CDK4/6抑制剂治疗所诱发关节症状的发生频率。
通过检索2005年1月1日至2021年1月1日的现有文献来确定符合条件的文章；该算法由以下关键词的预定义组合构成：“乳腺”“癌”“芳香化酶抑制剂”“CDK4/6”“Ⅲ期”。
本研究按照系统评价和Meta分析的首选报告项目（PRISMA）指南进行。所有评估第三代芳香化酶抑制剂（AIs）和CDK4/6抑制剂在绝经后女性转移性疾病中应用的随机对照Ⅲ期试验（RCTs）均被认为符合本评价的条件。
总体而言，共检索到16项随机对照试验（RCTs），其中9项研究探讨了AIs在转移性疾病中的应用，7项研究调查了CDK4/6抑制剂与AIs的联合应用。接受AIs治疗的患者中，1%至47%报告有关节痛，接受CDK4/6抑制剂治疗的患者中，5.8%至33.3%报告有关节痛。接受AIs治疗的患者中，2%至23.7%出现肌痛，而接受CDK4/6抑制剂治疗的患者中，这一比例为4.8%至11.9%。在接受AIs和CDK4/6抑制剂治疗的转移性疾病绝经后女性中，背痛的发生率分别为7%至32.9%和2.9%至8.5%。接受AIs治疗的绝经后女性中，7%至32.9%报告有骨痛，接受CDK4/6抑制剂治疗的女性中，这一比例为2.9%至8.5%。
AI治疗诱发的肌肉骨骼综合征是一种不良事件，影响超过三分之一（20%至47%）接受AIs治疗的绝经后患者，常导致治疗中断。随机对照试验的数据提供了证据，表明应用CDK4/6抑制剂后肌肉骨骼症状的发生率相对降低。CDK4/6抑制剂可能对AIMSS的发生具有保护作用。
