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

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

1 déc. 2020Breast Cancer Research

Auteurs

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

Résumé

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.