Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib
- Author(s)
- Zhu, Z; Turner, NC; Loi, S; Andre, F; Martin, M; Dieras, V; Gelmon, KA; Harbeck, N; Zhang, C; Cao, JQ; Yan, Z; Lu, DR; Wei, P; VanArsdale, TL; Rejto, PA; Huang, X; Rugo, HS; Loibl, S; Cristofanilli, M; Finn, RS; Liu, Y;
- Journal Title
- NPJ Precision Oncology
- Publication Type
- Research article
- 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).
- Department(s)
- Medical Oncology; Laboratory Research
- PubMed ID
- 35974168
- Publisher's Version
- https://doi.org/10.1038/s41698-022-00297-1
- Open Access at Publisher's Site
https://doi.org/10.1038/s41698-022-00297-1- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-05-16 05:12:22
Last Modified: 2025-05-16 05:13:40