Plasma thymidine kinase 1 activity and outcome of ER+ HER2- metastatic breast cancer patients treated with palbociclib and endocrine therapy.

Abstract

PURPOSE:

Previous cohort studies have reported plasma TK1 activity (pTKa) as a potential prognostic biomarker in estrogen receptor-positive (ER+) HER2-negative (HER2-) metastatic breast cancer (MBC). In this prospective study, we report here the prognostic impact of pTKa in ER+/HER2- MBC patients treated with endocrine therapy and CDK4/6 inhibitor.

EXPERIMENTAL DESIGN:

Patients were included into the prospective, ethics committee-approved ALCINA study (NCT02866149). Eligibility criteria were patients with ER+/HER2- MBC treated at Institut Curie with endocrine therapy and palbociclib. Plasma samples were obtained at baseline and after 4 weeks of treatment. pTKa was quantified by the DiviTum® assay (Biovica, Sweden).

RESULTS:

From May 2016 to August 2018, 103 patients treated with endocrine therapy and palbociclib were included. Patients had received a median of two prior systemic therapies for MBC (range 0-14). Median follow-up was 13.8 months (range 6-31), with median PFS and OS of 9.6 months (95%CI [7.0-11.3]) and 28 months (95%CI [23-not reached]), respectively. Median baseline pTKa was 292 Du/L (range 20-27,312 Du/L, IQR [89-853]). After adjusting for other prognostic factors, baseline pTKa remained an independent prognostic factor for both PFS (HR = 1.3 95%CI [1.1-1.4], p = 0.0005) and OS (HR = 1.3 95%CI [1.2-1.6], p < 0.0001), and 4-week pTKa was associated with OS (HR = 1.6 95%CI [1.3-2], p < 0.0001). That survival prediction was significantly improved by the addition of baseline pTKa to clinicopathological characteristics. Adding pTKa changes at 4 weeks to baseline pTKa did not further increase survival prediction.

CONCLUSION:

This study demonstrates the clinical validity of pTKa as a new circulating prognostic marker in ER+/HER2- MBC patients treated with endocrine therapy and palbociclib.

• Authors: Luc Cabel, Dan Rosenblum, Florence Lerebours, Etienne Brain, Delphine Loirat, Mattias Bergqvist, Paul Cottu, Anne Donnadieu, Anne Bethune, Nicolas Kiavue, Manuel Rodrigues, Jean-Yves Pierga, Marie-Laure Tanguy, François-Clément Bidard
• Journal: Breast cancer research : BCR (Breast Cancer Res) Vol. 22 Issue 1 Pg. 98 (09 14 2020) ISSN: 1465-542X [Electronic] England
• PMID: 32928264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• ESR1 protein, human
• Estrogen Receptor alpha
• Piperazines
• Pyridines
• Tamoxifen
• Fulvestrant
• Letrozole
• Thymidine Kinase
• thymidine kinase 1
• ERBB2 protein, human
• Receptor, ErbB-2
• palbociclib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (blood)
• Breast Neoplasms (blood, drug therapy, pathology)
• Estrogen Receptor alpha (metabolism)
• Female
• Fulvestrant (administration & dosage)
• Humans
• Letrozole (administration & dosage)
• Middle Aged
• Neoplasm Metastasis
• Piperazines (administration & dosage)
• Prognosis
• Prospective Studies
• Pyridines (administration & dosage)
• Receptor, ErbB-2 (metabolism)
• Survival Rate
• Tamoxifen (administration & dosage)
• Thymidine Kinase (blood)