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

Breast Cancer Res. 2020 Sep 14;22(1):98. doi: 10.1186/s13058-020-01334-2.

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.

Keywords: Biomarker; CDK4/6 inhibitor; Metastatic breast cancer; Palbociclib; Thymidine kinase 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / 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*

Substances

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

Associated data

  • ClinicalTrials.gov/NCT02866149