Kanjanapan Yada, Anderson Wayne, Smith Mirka, Green Jenny, Chalker Elizabeth, Craft Paul
Department of Medical Oncology, The Canberra Hospital, Canberra, Australia; Australian National University Medical School, Australian National University, Canberra, Australia.
Epidemiology Section, Data Analytics Branch, Australian Capital Territory Health Directorate, Canberra, Australia.
Clin Breast Cancer. 2025 Feb;25(2):e159-e169.e2. doi: 10.1016/j.clbc.2024.08.022. Epub 2024 Aug 29.
Adjuvant CDK4/6 inhibitors abemaciclib and ribociclib improved disease-free survival (DFS) added to endocrine therapy in hormone receptor (HR)-positive HER2-negative early breast cancer (EBC), in monarchE (NCT03155997) and NATALEE (NCT03701334) trials respectively. We assessed the proportion and outcome of EBC patients qualifying for adjuvant CDK4/6 inhibitors in the real-world.
Consecutive female patients with HR-positive HER2-negative EBC between 1997 and 2017 from the Australian Capital Territory and South-East New South Wales Breast Cancer Treatment Group registry were analyzed. Patients eligible for abemaciclib had ≥4 axillary nodes involved or 1-3 nodes plus primary >5 cm or grade 3. Ribociclib eligibility was defined as node-positive and node-negative with primary >5 cm or >2 cm grade 3.
Of 3840 patients, 671 (17.5%) were abemaciclib-eligible and 1587 (41.3%) ribociclib-eligible . The 5-year DFS was 77% and 94% in abemaciclib-eligible and noneligible registry patients respectively (HR 2.6, 95% CI 2.26-3.05, P < .001). The 5-year DFS was 86% and 97% in ribociclib-eligible and noneligible registry patients respectively (HR 1.92, 95% CI 1.67-2.19, P < .001). Compared with monarchE trial patients, abemaciclib-eligible registry patients were older (median 55 years in registry vs. 51 years in trial), with lower nodal burden (≥4 nodes in 44% in registry vs. 60% in trial). There were more stage III cancers in NATALEE trial patients (60%) than ribociclib-eligible registry patients (24%).
Many women with EBC will qualify for adjuvant CDK4/6 inhibitors (17.5% abemaciclib, 41.3% ribociclib) with resource and workforce implications. In the real-world setting, a greater proportion of adjuvant CDK4/6-eligible patients have lower stage disease, therefore the absolute benefit from treatment may be smaller than estimated by the trials.
在monarchE（NCT03155997）和NATALEE（NCT03701334）试验中，辅助性CDK4/6抑制剂阿贝西利和瑞博西尼分别联合内分泌治疗可改善激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性早期乳腺癌（EBC）患者的无病生存期（DFS）。我们评估了在现实世界中有资格接受辅助性CDK4/6抑制剂治疗的EBC患者的比例及预后情况。
分析了1997年至2017年来自澳大利亚首都地区和新南威尔士州东南部乳腺癌治疗组登记处的连续HR阳性、HER2阴性EBC女性患者。有资格使用阿贝西利的患者需有≥4个腋窝淋巴结受累或1 - 3个淋巴结且原发肿瘤>5 cm或为3级。瑞博西尼的适用标准为淋巴结阳性以及淋巴结阴性但原发肿瘤>5 cm或>2 cm且为3级。
在3840例患者中，671例（17.5%）有资格使用阿贝西利，1587例（41.3%）有资格使用瑞博西尼。在有资格使用阿贝西利的登记处患者和无资格使用的登记处患者中，5年DFS分别为77%和94%（风险比[HR] 2.6，95%置信区间[CI] 2.26 - 3.05，P <.001）。在有资格使用瑞博西尼的登记处患者和无资格使用的登记处患者中，5年DFS分别为86%和97%（HR 1.92，95% CI 1.67 - 2.19，P <.001）。与monarchE试验患者相比，有资格使用阿贝西利的登记处患者年龄更大（登记处患者中位年龄55岁，试验中为51岁），淋巴结负担更低（登记处44%的患者有≥4个淋巴结，试验中为60%）。NATALEE试验患者中III期癌症患者比例（60%）高于有资格使用瑞博西尼的登记处患者（24%）。
许多EBC女性患者有资格接受辅助性CDK4/6抑制剂治疗（17.5%有资格使用阿贝西利，41.3%有资格使用瑞博西尼），这对资源和人力有影响。在现实世界中，有资格接受辅助性CDK4/6治疗的患者中更大比例为疾病分期较低者，因此治疗的绝对获益可能小于试验估计值。
