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ePoster

12P - Gene expression profiling in early breast cancer treated with neoadjuvant ribociclib plus letrozole (R+L) versus chemotherapy (CT): A correlative analysis of the SOLTI-1402/CORALLEEN phase II trial

Date

24 May 2020

Session

ePoster

Presenters

Nuria Chic

Citation

Annals of Oncology (2020) 31 (suppl_2): S15-S41. 10.1016/annonc/annonc117

Authors

N. Chic1, B. González-Farré2, L. Paré3, T. Pascual3, C. Saura Manich4, C. Hernando Melia5, M. Muñoz6, P. Fernandez7, D. Martínez8, E. Sanfeliu2, F. Brasó-Maristany9, X. González-Farré10, A.M. Antunes De Melo e Oliveira11, M. Gil-Gil12, P. Celiz3, E.M. Ciruelos13, P. Villagrasa14, J. Gavila Gregori15, A. Prat16

Author affiliations

  • 1 Medical Oncology, Hospital Clinic, 08036 - Barcelona/ES
  • 2 Pathology, Hospital Clinic of Barcelona, 08036 - Barcelona/ES
  • 3 Dept. Scientific, SOLTI Breast Cancer Research Group, 08008 - Barcelona/ES
  • 4 Dept. Medical Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 5 Valencia, Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES
  • 6 Dept. Medical Oncology, Hospital Clinic of Barcelona, 08036 - Barcelona/ES
  • 7 Dept. Of Pathology, Hospital Germans Trias i Pujol, 08916 - Badalona/ES
  • 8 Dept. Scientific, Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, 08036 - Barcelona/ES
  • 9 Translational Genomics And Targeted Therapeutics In Solid Tumors, IDIBAPS, 08036 - Barcelona/ES
  • 10 Dept. Medical Oncology, Hospital General de Catalunya, 08195 - San Cugat del Valles/ES
  • 11 Dept. Medical Oncology, Vall d' Hebron University Hospital;; Vall d’Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 12 Dept. Medical Oncology, Institut Catala d’ Oncologia, 08908 - L'Hospitalet de Llobregat/ES
  • 13 Dept. Medical Oncology, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 14 Breast Cancer Research Group, SOLTI, 08008 - Barcelona/ES
  • 15 Dept. Medical Oncology, IVO - Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 16 Medical Oncology Department, Hospital Clinic y Provincial de Barcelona, 08036 - Barcelona/ES
More

Abstract 12P

Background

In the CORALLEEN trial, R+L achieved similar response rates to multi-agent CT. We present a comprehensive gene expression analysis done before, during, and after therapy to fully characterize the biology behind the primary results of the trial.

Methods

CORALLEEN was a randomized study in postmenopausal women with stage I-IIIA hormone receptor positive (HR+)/HER2-negative Luminal B breast cancer by PAM50. Patients (pts) received either 6 cycles of R+L or 4 cycles of AC followed by 12 doses of paclitaxel. Primary endpoint was rate of PAM50 Risk of Relapse (ROR) low disease at surgery. Baseline, week 2, and surgical specimens were collected. Expression of 770 genes and 31 signatures were determined using the Breast360TM nCounter-based codeset. Response was defined as ROR-low disease at surgery, relative/absolute changes in ROR between baseline/week 2 and surgery, RCB-0/I or levels of Ki67 at surgery. To identify genes associated with response, a significance of microarrays (SAM) analysis with a false discovery rate (FDR) <5% was performed.

Results

A total 297/318 (93.4%) samples were available. No genes or signatures at baseline, or week 2, were found to be associated with response at surgery in each arm. At week 2, 146 (14.6%) genes or signatures were found significantly up-regulated (n=47) and down-regulated (n=99) in the R+L arm compared to CT. R+L induced higher expression of genes related to DNA damage repair and immune activation (e.g. TP53, RAD52, GZMM and CD19) and lower expression of cell-cycle and hormone-related genes (e.g. PGR, CDK1 and MKI67). At surgery, 102 (10.2%) genes or signatures were found significantly up-regulated (n=4) and down-regulated (n=98) in the R+L arm compared to CT. R+L induced higher downregulation of estrogen- and proliferation-related genes and signatures (e.g. PGR, ER signaling, and MKI67).

Conclusions

No genes were able to predict response. Compared to CT, R+L induced higher downregulation of proliferation-related genes and signatures at week 2 and surgery. These results support the strategy to use the neoadjuvant setting to select patients who achieve a large molecular downstaging following CDK4/6 inhibition.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

SOLTI Breast Cancer Research Group.

Funding

Novartis, Nanostring, Breast Cancer Research Foundation-AACR Career Development Award (to AP), PhD4MD grant (to NC), Fundación Científica Asociación Española Contra el Cáncer - Ayuda Postdoctoral AECC 2017 (to FB-M), This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant agreement No. 847912.

Disclosure

N. Chic: Travel/Accommodation/Expenses: Novartis. C. Saura: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Puma biotechnology; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi-Sankyo; Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy, Travel/Accommodation/Expenses: Genomyc Health; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Synthon biopharmaceuticals; Research grant/Funding (institution): Roche-Genentech; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Piqur; Research grant/Funding (institution): BMS. M. Muñoz: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Breast Cancer Research Foundation-AACR; Research grant/Funding (institution): Breast Cancer Now Career Catalyst; Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Lilly. X. González-Farré: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Eisai. M. Oliveira: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Puma Biotechnology; Research grant/Funding (institution): Philips Healthcare; Travel/Accommodation/Expenses: Grünenthal Group; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: GP Pharm. M. Gil-Gil: Honoraria (self): Genentech; Honoraria (self): Novartis; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Daiichi; Honoraria (self): Eisai; Travel/Accommodation/Expenses: Roche. E.M. Ciruelos: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer. P. Villagrasa: Speaker Bureau/Expert testimony: NanoString. J. Gavila Gregori: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche. A. Prat: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Lilly; Advisory/Consultancy: NanoString; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Oncolytics; Advisory/Consultancy: Daiichi; Advisory/Consultancy: Puma; Advisory/Consultancy: BMS. All other authors have declared no conflicts of interest.

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