biostudies-literatureUnknown6(1)Zhu ZWhile cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, combined with endocrine therapy (ET), are becoming the standard-of-care for hormone receptor–positive/human epidermal growth factor receptor 2‒negative metastatic breast cancer, further mechanistic insights are needed to maximize benefit from the treatment regimen. Herein, we conducted a systematic comparative analysis of gene expression/progression-free survival relationship from two phase 3 trials (PALOMA-2 [first-line] and PALOMA-3 [≥second-line]). In the ET-only arm, there was no inter-therapy line correlation. However, adding palbociclib resulted in concordant biomarkers independent of initial ET responsiveness, with shared sensitivity genes enriched in estrogen response and resistance genes over-representedNPJ precision oncologyhttps://www.ebi.ac.uk/biostudies/studies/S-EPMC9381541biostudies-literatureComparative biomarker analysis of PALOMA-2/3 trials for palbociclibPMC9381541Gelmon KHarbeck NZhu ZCristofanilli MCao JRejto PLu DVanArsdale TAndre FDieras VLiu YWei PYan ZHuang XTurner NLoibl SLoi SMartin MFinn RZhang CRugo HfalseComparative biomarker analysis of PALOMA-2/3 trials for palbociclibWhile cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, combined with endocrine therapy (ET), are becoming the standard-of-care for hormone receptor–positive/human epidermal growth factor receptor 2‒negative metastatic breast cancer, further mechanistic insights are needed to maximize benefit from the treatment regimen. Herein, we conducted a systematic comparative analysis of gene expression/progression-free survival relationship from two phase 3 trials (PALOMA-2 [first-line] and PALOMA-3 [≥second-line]). In the ET-only arm, there was no inter-therapy line correlation. However, adding palbociclib resulted in concordant biomarkers independent of initial ET responsiveness, with shared sensitivity genes enriched in estrogen response and resistance genes over-represented2022-01-01T00:00:00Z2022 Jan2025-04-04T11:33:30.454Z2025-02-19T05:05:59.282ZS-EPMC9381541