Abstract | PURPOSE: EXPERIMENTAL DESIGN: To determine markers of sensitivity and resistance to palbociclib plus letrozole, we performed comprehensive biomarker analyses, investigating the correlation with progression-free survival (PFS), on baseline tumor tissues from PALOMA-2. RESULTS: Despite a broad biomarker search, palbociclib plus letrozole demonstrated consistent PFS gains versus placebo plus letrozole, with no single biomarker or cassette of markers associated with lack of benefit from combination treatment. Palbociclib plus letrozole confers efficacy on both luminal A and B patients. Higher CDK4 levels were associated with endocrine resistance which was mitigated by the addition of palbociclib, whereas lower PD-1 levels were associated with greater palbociclib plus letrozole benefit. Tumors with more active growth factor signaling, as exemplified by increased expression of FGFR2 and ERBB3 mRNA, appeared to be associated with greater PFS gain from the addition of palbociclib. CONCLUSIONS: These data underscore the importance of CDK4/6 signaling in HR+/HER2- breast cancer and suggest that the interplay between steroid hormone and peptide growth factor signaling could drive dependence on CDK4/6 signaling.See related commentary by Anurag et al., p. 3.
|
Authors | Richard S Finn, Yuan Liu, Zhou Zhu, Miguel Martin, Hope S Rugo, Véronique Diéras, Seock-Ah Im, Karen A Gelmon, Nadia Harbeck, Dongrui R Lu, Eric Gauthier, Cynthia Huang Bartlett, Dennis J Slamon |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 26
Issue 1
Pg. 110-121
(01 01 2020)
ISSN: 1557-3265 [Electronic] United States |
PMID | 31527167
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Comment)
|
Copyright | ©2019 American Association for Cancer Research. |
Chemical References |
- Receptors, Estrogen
- Letrozole
- Receptor, ErbB-2
- CDK4 protein, human
- Cyclin-Dependent Kinase 4
|
Topics |
- Antineoplastic Combined Chemotherapy Protocols
- Cyclin-Dependent Kinase 4
- Female
- Humans
- Letrozole
- Receptor, ErbB-2
- Receptors, Estrogen
|