Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib.

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).

• Authors: Zhou Zhu, Nicholas C Turner, Sherene Loi, Fabrice André, Miguel Martin, Véronique Diéras, Karen A Gelmon, Nadia Harbeck, Cathy Zhang, Joan Q Cao, Zhengming Yan, Dongrui R Lu, Ping Wei, Todd L VanArsdale, Paul A Rejto, Xin Huang, Hope S Rugo, Sibylle Loibl, Massimo Cristofanilli, Richard S Finn, Yuan Liu
• Journal: NPJ precision oncology (NPJ Precis Oncol) Vol. 6 Issue 1 Pg. 56 (Aug 16 2022) ISSN: 2397-768X [Print] England
• PMID: 35974168 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).