Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/214027
Title: | Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients |
Author: | Pascual, Javier Gil-gil, Miguel Proszek, Paula Zielinski, Christoph Reay, Alistair Ruiz-borrego, Manuel Cutts, Rosalind Ciruelos Gil, Eva M. Feber, Andrew Muñoz-mateu, Montserrat Swift, Claire Bermejo, Begoña Herranz, Jesus Margeli Vila, Mireia Antón, Antonio Kahan, Zsuzsanna Csöszi, Tibor Liu, Yuan Fernandez-garcia, Daniel Garcia-murillas, Isaac Hubank, Michael Turner, Nicholas C. Martín, Miguel |
Issue Date: | 25-Jul-2023 |
Publisher: | American Association for Cancer Research (AACR) |
Abstract: | Purpose: Prognostic and predictive biomarkers to cyclindependent kinases 4 and 6 inhibitors are lacking. Circulating tumor DNA ( ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy. Experimental Design: Correlative blood samples were collected at baseline [cycle 1-day 1 (C1D1)] and prior to treatment [cycle 1-day 15 (C1D15)]. Plasma ctDNA was sequenced with a custom error-corrected capture panel, with both univariate and multivariate Cox models used for treatment efficacy associations. A prespecified methodology measuring ctDNA changes in clonal mutations between C1D1 and C1D15 was used for the on-treatment ctDNA dynamic model. Results: 201 patients were profiled at baseline, with ctDNA detection associated with worse progression-free survival (PFS)/ overall survival (OS). Detectable TP53 mutation showed worse PFS and OS in both treatment arms, even after restricting population to baseline ctDNA detection. ESR1 mutations were associated with worse OS overall, which was lost when restricting population to baseline ctDNA detection. PIK3CA mutations confer worse OS only to patients on the palbociclib+fulvestrant treatment arm. ctDNA dynamics analysis (n = 120) showed higher ctDNA suppression in the capecitabine arm. Patients without ctDNA suppression showed worse PFS in both treatment arms. Conclusions: We show impaired survival irrespective of endocrine or chemotherapy-based treatments for patients with hormone receptor-positive/HER2-negative metastatic breast cancer harboring plasma TP53 mutations. Early ctDNA suppression may provide treatment efficacy predictions. Further validation to fully demonstrate clinical utility of ctDNA dynamics is warranted. |
Note: | Reproducció del document publicat a: https://doi.org/10.1158/1078-0432.CCR-23-0956 |
It is part of: | Clinical Cancer Research, 2023, vol. 29, issue. 20, p. 4166-4177 |
URI: | http://hdl.handle.net/2445/214027 |
Related resource: | https://doi.org/10.1158/1078-0432.CCR-23-0956 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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