Fasching Peter A, Delea Thomas E, Lu Yen-Shen, De Boer Richard, Hurvitz Sara A, Moynahan Aaron, Chandiwana David, Lanoue Brad, Hu Huilin, Thuerigen Astrid, O'Shaughnessy Joyce
University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Department of Gynecology and Obstetrics, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Policy Analysis Inc. (PAI), Brookline, MA, USA.
Cancer Manag Res. 2021 Nov 1;13:8179-8189. doi: 10.2147/CMAR.S325043. eCollection 2021.
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus endocrine therapy are recommended for first-line treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). However, not all CDK4/6i trials have reported significant overall survival (OS) benefit, and there have been no head-to-head trials. Two trials have reported OS outcomes in first-line patients: MONALEESA-3 reported significant OS benefit with first- or second-line ribociclib plus fulvestrant (RIB+FUL) versus placebo plus fulvestrant (PBO+FUL), while PALOMA-1 reported no significant OS benefit for palbociclib plus letrozole (PAL+LET) versus LET in first-line postmenopausal patients. Matched-adjusted indirect comparisons (MAICs) are an established method for comparing efficacy of treatments from different trials. We used an MAIC to compare first-line patients from MONALEESA-3 and PALOMA-1.
An unanchored MAIC of progression-free survival (PFS) and OS in first-line patients with HR+/HER2- ABC treated with RIB+FUL versus PAL+LET was conducted using individual patient data from MONALEESA-3 and aggregated data from PALOMA-1. To match patients in PALOMA-1, patients in MONALEESA-3 were limited to those with no prior endocrine therapy for ABC and no (neo) adjuvant LET ≤12 months before enrollment. PFS and OS were compared using Kaplan-Meier estimators and Cox regression.
A total of 329 and 178 patients from RIB+FUL and PBO+FUL arms, respectively, of MONALEESA-3 were matched to 84 and 81 patients from PAL+LET and LET arms of PALOMA-1. After weighting, OS was significantly longer for RIB+FUL versus PAL+LET (hazard ratio [HR], 0.50; 95% CI, 0.32-0.77; = 0.0020). PFS favored RIB+FUL versus PAL+LET, although the difference was not statistically significant (HR, 0.77; 95% CI, 0.54-1.10; = 0.1553).
Using MAIC to adjust for trial differences, OS comparisons favored RIB+FUL over PAL+LET as first-line treatment in postmenopausal patients with HR+/HER2- ABC. These exploratory results suggest a significant increase in OS benefit with RIB treatment compared with PAL.
细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）联合内分泌治疗被推荐用于激素受体阳性/人表皮生长因子受体2阴性（HR+/HER2-）晚期乳腺癌（ABC）的一线治疗。然而，并非所有CDK4/6i试验都报告了显著的总生存期（OS）获益，且尚无头对头试验。两项试验报告了一线患者的OS结果：MONALEESA-3报告，一线或二线使用瑞博西尼联合氟维司群（RIB+FUL）对比安慰剂联合氟维司群（PBO+FUL）有显著的OS获益；而PALOMA-1报告，在一线绝经后患者中，帕博西尼联合来曲唑（PAL+LET）对比来曲唑（LET）无显著的OS获益。匹配调整间接比较（MAIC）是一种比较不同试验中治疗效果的既定方法。我们使用MAIC比较了MONALEESA-3和PALOMA-1中的一线患者。
使用MONALEESA-3的个体患者数据和PALOMA-1的汇总数据，对HR+/HER2- ABC一线患者接受RIB+FUL与PAL+LET治疗的无进展生存期（PFS）和OS进行非锚定MAIC。为匹配PALOMA-1中的患者，MONALEESA-3中的患者仅限于那些未接受过ABC内分泌治疗且在入组前无（新）辅助来曲唑治疗≤12个月的患者。使用Kaplan-Meier估计量和Cox回归比较PFS和OS。
MONALEESA-3中分别来自RIB+FUL和PBO+FUL组的329例和178例患者与PALOMA-1中来自PAL+LET和LET组的84例和81例患者相匹配。加权后，RIB+FUL组的OS显著长于PAL+LET组（风险比[HR]，0.50；95%置信区间，0.32 - 0.77；P = 0.0020）。PFS倾向于RIB+FUL而非PAL+LET，尽管差异无统计学意义（HR，0.77；95%置信区间，0.54 - 1.10；P = 0.1553）。
使用MAIC调整试验差异后，在HR+/HER2- ABC绝经后患者的一线治疗中，OS比较显示RIB+FUL优于PAL+LET。这些探索性结果表明，与PAL相比，RIB治疗的OS获益显著增加。
