Francesco Schettini, Sabrina Nucera, Giuseppe Di Grazia, Fabiola Giudici, Carla Strina, Manuela Milani, Richard Tancredi, Benedetta Conte, Carmen Criscitiello, Mario Giuliano, Matteo Lambertini, Rodrigo Sánchez-Bayona, Tomás Pascual, Grazia Arpino, Lucia Del Mastro, Paolo Vigneri, Massimo Cristofanilli, Hope S Rugo, Alessandra Gennari, Giuseppe Curigliano, Daniele Generali
{"title":"帕博西尼+内分泌治疗在hr阳性/ her2阴性MBC中的实际研究和随机研究的比较疗效:系统评价和荟萃分析。","authors":"Francesco Schettini, Sabrina Nucera, Giuseppe Di Grazia, Fabiola Giudici, Carla Strina, Manuela Milani, Richard Tancredi, Benedetta Conte, Carmen Criscitiello, Mario Giuliano, Matteo Lambertini, Rodrigo Sánchez-Bayona, Tomás Pascual, Grazia Arpino, Lucia Del Mastro, Paolo Vigneri, Massimo Cristofanilli, Hope S Rugo, Alessandra Gennari, Giuseppe Curigliano, Daniele Generali","doi":"10.1093/jncics/pkaf083","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>RW data confirm palbociclib+endocrine therapy effectiveness, reinforcing its applicability to broader patient populations.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":4.1000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413244/pdf/","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Francesco Schettini, Sabrina Nucera, Giuseppe Di Grazia, Fabiola Giudici, Carla Strina, Manuela Milani, Richard Tancredi, Benedetta Conte, Carmen Criscitiello, Mario Giuliano, Matteo Lambertini, Rodrigo Sánchez-Bayona, Tomás Pascual, Grazia Arpino, Lucia Del Mastro, Paolo Vigneri, Massimo Cristofanilli, Hope S Rugo, Alessandra Gennari, Giuseppe Curigliano, Daniele Generali\",\"doi\":\"10.1093/jncics/pkaf083\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>RW data confirm palbociclib+endocrine therapy effectiveness, reinforcing its applicability to broader patient populations.</p>\",\"PeriodicalId\":14681,\"journal\":{\"name\":\"JNCI Cancer Spectrum\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413244/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JNCI Cancer Spectrum\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/jncics/pkaf083\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JNCI Cancer Spectrum","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/jncics/pkaf083","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.
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.