Goetz Matthew P, Okera Meena, Wildiers Hans, Campone Mario, Grischke Eva-Maria, Manso Luis, André Valérie A M, Chouaki Nadia, San Antonio Belén, Toi Masakazu, Sledge George W
Department of Oncology, Mayo Clinic, 200 First St. S.W, Rochester, MN, 55905, USA.
Adelaide Cancer Center, Adelaide, Australia.
Breast Cancer Res Treat. 2021 Apr;186(2):417-428. doi: 10.1007/s10549-020-06029-y. Epub 2021 Jan 3.
Abemaciclib in combination with endocrine therapy (ET) has demonstrated significant efficacy benefits in HR+ , HER2- advanced breast cancer patients in the Phase 3 studies MONARCH 2 (fulvestrant as ET) and MONARCH 3 (letrozole or anastrozole as ET). Here, we report age-specific safety and efficacy outcomes.
Exploratory analyses of MONARCH 2 and 3 were performed for 3 age groups (<65, 65-74, and ≥75 years). For safety, data were pooled from both studies; for efficacy, a subgroup analysis of PFS was performed for each trial independently.
Pooled safety data were available for 1152 patients. Clinically relevant diarrhea (Grade 2/3) was higher in older patients receiving abemaciclib + ET (<65, 39.5%; 65-74, 45.2%; ≥75, 55.4%) versus placebo + ET (<65, 6.8%; 65-74, 4.5%; ≥75, 16.0%). Nausea, decreased appetite, and venous thromboembolic events were all moderately higher in older patients. Neutropenia (Grade ≥ 3) did not differ as a function of age in the abemaciclib + ET arm (<65, 25.8%; 65-74, 27.4%; ≥75, 18.1%). Dose adjustments and discontinuation rates were slightly higher in older patients. Abemaciclib + ET improved PFS compared with placebo + ET independent of patient age, with no significant difference in abemaciclib treatment effect between the 3 age groups (MONARCH 2: interaction p-value, 0.695; MONARCH 3: interaction p-value, 0.634). Estimated hazard ratios ranged from 0.523-0.633 (MONARCH 2) and 0.480-0.635 (MONARCH 3).
While higher rates of adverse events were reported in older patients, they were manageable with dose adjustments and concomitant medication. Importantly, a consistent efficacy benefit was observed across all age groups.
ClinicalTrials.gov: NCT02107703 (first posted April 8, 2014) and NCT02246621 (first posted September 23, 2014).
在3期研究MONARCH 2（以氟维司群作为内分泌治疗）和MONARCH 3（以来曲唑或阿那曲唑作为内分泌治疗）中，阿贝西利联合内分泌治疗（ET）已在激素受体阳性（HR+）、人表皮生长因子受体2阴性（HER2-）的晚期乳腺癌患者中显示出显著的疗效优势。在此，我们报告特定年龄的安全性和疗效结果。
对MONARCH 2和3进行探索性分析，分为3个年龄组（<65岁、65 - 74岁和≥75岁）。对于安全性，数据来自两项研究的汇总；对于疗效，对每项试验分别进行无进展生存期（PFS）的亚组分析。
有1152例患者的汇总安全性数据。接受阿贝西利 + ET的老年患者中临床相关腹泻（2/3级）发生率更高（<65岁，39.5%；65 - 74岁，45.2%；≥75岁，55.4%），而接受安慰剂 + ET的患者中该发生率为（<65岁，6.8%；65 - 74岁，4.5%；≥75岁，16.0%）。老年患者中恶心、食欲减退和静脉血栓栓塞事件的发生率也均略高。在阿贝西利 + ET组中，3级及以上中性粒细胞减少症的发生率在不同年龄组中无差异（<65岁，25.8%；65 - 74岁，27.4%；≥75岁，18.1%）。老年患者的剂量调整和停药率略高。与安慰剂 + ET相比，阿贝西利 + ET可改善PFS，且与患者年龄无关，3个年龄组之间阿贝西利的治疗效果无显著差异（MONARCH 2：交互作用P值，0.695；MONARCH 3：交互作用P值，0.634）。估计风险比范围为0.523 - 0.633（MONARCH 2）和0.480 - 0.635（MONARCH 3）。
虽然老年患者报告的不良事件发生率较高，但可通过剂量调整和辅助用药进行管理。重要的是，在所有年龄组中均观察到一致的疗效优势。
ClinicalTrials.gov：NCT02107703（首次发布于2014年4月8日）和NCT02246621（首次发布于2014年9月23日）。
