哌柏西利联合内分泌治疗在激素受体阳性/人表皮生长因子受体2阴性转移性乳腺癌中的真实世界研究与随机对照研究的疗效比较：系统评价与荟萃分析
Comparative efficacy between real-world and randomized studies of palbociclib+endocrine therapy in HR-positive/HER2-negative metastatic breast cancer: systematic review and meta-analysis.
作者信息
Schettini Francesco, Nucera Sabrina, Di Grazia Giuseppe, Giudici Fabiola, Strina Carla, Milani Manuela, Tancredi Richard, Conte Benedetta, Criscitiello Carmen, Giuliano Mario, Lambertini Matteo, Sánchez-Bayona Rodrigo, Pascual Tomás, Arpino Grazia, Del Mastro Lucia, Vigneri Paolo, Cristofanilli Massimo, Rugo Hope S, Gennari Alessandra, Curigliano Giuseppe, Generali Daniele
机构信息
Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
Department of Medical Oncology, Clinic Barcelona Comprehensive Cancer Center, Barcelona, Spain.
出版信息
JNCI Cancer Spectr. 2025 Sep 1;9(5). doi: 10.1093/jncics/pkaf083.
BACKGROUND
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard-of-care for hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC). Palbociclib, the first approved CDK4/6i, significantly improved progression-free survival (PFS) in randomized controlled trials (RCTs). However, real-world (RW) outcomes may differ due to broader patient populations. This meta-analysis evaluates the applicability of pivotal RCT findings to RW settings.
METHODS
We conducted a systematic review and meta-analysis of RW studies on HR+/HER2- MBC treated with palbociclib+aromatase inhibitors (AI) or fulvestrant, reporting median PFS (mPFS) and/or overall survival (mOS). Pooled mPFS/OS was estimated using the median of medians (MM) and weighted MM (WM). RW estimates were deemed comparable to RCTs if MMPFS/OS or WMPFS/OS fell within RCTs' 95% confidence intervals (CIs). Similar criteria applied to pooled hazard ratios (HRs) of PFS/OS for palbociclib+AI vs AI in visceral/nonvisceral subgroups.
RESULTS
Twelve RW studies were analyzed. First-line palbociclib+AI MMPFS (22.5 months, 95% CI = 19.5 to 31.8) aligned with PALOMA-1/2 pooled mPFS (23.9, 95% CI = 20.2 to 27.6). First-line palbociclib+fulvestrant MMPFS (13.5, 95% CI = 11.6 to 28.5) exceeded PALOMA-3 (11.2, 95% CI = 9.5 to 12.9). Second-line palbociclib+fulvestrant MMPFS (11.5 months, 95% CI = 6.3 to 15.3) was consistent with PALOMA-3. RW first-line mOS (51.2 months, 95% CI = 49.1 to 53.3) surpassed PALOMA-1/2 pooled mOS (45.7, 95% CI = 37.5 to 53.8). WMOS (49.1 months, 95% CI = 49.1 to 53.3) was slightly lower than RCTs (53.7, 95% CI = 37.5 to 53.8). Palbociclib+AI outperformed AI in RW visceral disease, aligning with RCTs, and showed heterogeneous but favorable benefit in nonvisceral disease.
CONCLUSIONS
RW data confirm palbociclib+endocrine therapy effectiveness, reinforcing its applicability to broader patient populations.
背景
细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）联合内分泌治疗是激素受体阳性（HR+）/人表皮生长因子受体2阴性（HER2-）转移性乳腺癌（MBC）的标准治疗方案。首个获批的CDK4/6i哌柏西利在随机对照试验（RCT）中显著改善了无进展生存期（PFS）。然而，由于患者群体更广泛，真实世界（RW）中的结果可能有所不同。本荟萃分析评估了关键RCT结果在RW环境中的适用性。
方法
我们对使用哌柏西利+芳香化酶抑制剂（AI）或氟维司群治疗的HR+/HER2-MBC的RW研究进行了系统评价和荟萃分析，报告了中位PFS（mPFS）和/或总生存期（mOS）。使用中位数的中位数（MM）和加权MM（WM）估计合并的mPFS/OS。如果MMPFS/OS或WMPFS/OS落在RCT的95%置信区间（CI）内，则认为RW估计值与RCT具有可比性。类似的标准适用于哌柏西利+AI与AI在内脏/非内脏亚组中的PFS/OS合并风险比（HR）。
结果
分析了12项RW研究。一线哌柏西利+AI的MMPFS（22.5个月，95%CI = 19.5至31.8）与PALOMA-1/2合并的mPFS（23.9，95%CI = 20.2至27.6）一致。一线哌柏西利+氟维司群的MMPFS（13.5，95%CI = 11.6至28.5）超过了PALOMA-3（11.2，95%CI = 9.5至12.9）。二线哌柏西利+氟维司群的MMPFS（11.5个月，95%CI = 6.3至15.3）与PALOMA-3一致。RW一线mOS（51.2个月，95%CI = 49.1至53.3）超过了PALOMA-1/2合并的mOS（45.7，95%CI = 37.5至53.8）。WMOS（49.1个月，95%CI = 49.1至53.3）略低于RCT（53.7，95%CI = 37.5至53.8）。在RW内脏疾病中，哌柏西利+AI优于AI，与RCT一致，并且在非内脏疾病中显示出异质性但有利的益处。
结论
RW数据证实了哌柏西利+内分泌治疗的有效性，加强了其在更广泛患者群体中的适用性。
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