1. Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib.
- Author
-
Zhu, Zhou, Turner, Nicholas C., Loi, Sherene, André, Fabrice, Martin, Miguel, Diéras, Véronique, Gelmon, Karen A., Harbeck, Nadia, Zhang, Cathy, Cao, Joan Q., Yan, Zhengming, Lu, Dongrui R., Wei, Ping, VanArsdale, Todd L., Rejto, Paul A., Huang, Xin, Rugo, Hope S., Loibl, Sibylle, Cristofanilli, Massimo, and Finn, Richard S.
- Subjects
EPIDERMAL growth factor receptors ,CLINICAL trials ,METASTATIC breast cancer ,CYCLIN-dependent kinase inhibitors ,COMPARATIVE studies - Abstract
While 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-represented by mTORC1 signaling and G2/M checkpoint. Biomarker patterns from the combination arm resembled patterns observed in ET in advanced treatment-naive patients, especially patients likely to be endocrine-responsive. Our findings suggest palbociclib may recondition endocrine-resistant tumors to ET, and may guide optimal therapeutic sequencing by partnering CDK4/6 inhibitors with different ETs. Pfizer (NCT01740427; NCT01942135). [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF