COGNITION: a prospective precision oncology trial for patients with early breast cancer at high risk following neoadjuvant chemotherapy.

Abstract

BACKGROUND:

COGNITION (Comprehensive assessment of clinical features, genomics and further molecular markers to identify patients with early breast cancer for enrolment on marker driven trials) is a diagnostic registry trial that employs genomic and transcriptomic profiling to identify biomarkers in patients with early breast cancer with a high risk for relapse after standard neoadjuvant chemotherapy (NACT) to guide genomics-driven targeted post-neoadjuvant therapy.

PATIENTS AND METHODS:

At National Center for Tumor Diseases Heidelberg patients were biopsied before starting NACT, and for patients with residual tumors after NACT additional biopsy material was collected. Whole-genome/exome and transcriptome sequencing were applied on tumor and corresponding blood samples.

RESULTS:

In the pilot phase 255 patients were enrolled, among which 213 were assessable: thereof 48.8% were identified to be at a high risk for relapse following NACT; 86.4% of 81 patients discussed in the molecular tumor board were eligible for a targeted therapy within the interventional multiarm phase II trial COGNITION-GUIDE (Genomics-guided targeted post neoadjuvant therapy in patients with early breast cancer) starting enrolment in Q4/2022. An in-depth longitudinal analysis at baseline and in residual tumor tissue of 16 patients revealed some cases with clonal evolution but largely stable genetic alterations, suggesting restricted selective pressure of broad-acting cytotoxic neoadjuvant chemotherapies.

CONCLUSIONS:

While most precision oncology initiatives focus on metastatic disease, the presented concept offers the opportunity to empower novel therapy options for patients with high-risk early breast cancer in the post-neoadjuvant setting within a biomarker-driven trial and provides the basis to test the value of precision oncology in a curative setting with the overarching goal to increase cure rates.

• Authors: C Pixberg, M Zapatka, M Hlevnjak, S Benedetto, J P Suppelna, J Heil, K Smetanay, L Michel, C Fremd, V Körber, M Rübsam, L Buschhorn, S Heublein, B Schäfgen, M Golatta, C Gomez, A von Au, M Wallwiener, S Wolf, N Dikow, C Schaaf, E Gutjahr, M Allgäuer, A Stenzinger, K Pfütze, R Kirsten, D Hübschmann, H-P Sinn, D Jäger, A Trumpp, R Schlenk, T Höfer, V Thewes, A Schneeweiss, P Lichter
• Journal: ESMO open (ESMO Open) Vol. 7 Issue 6 Pg. 100637 (12 2022) ISSN: 2059-7029 [Electronic] England
• PMID: 36423362 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Topics

• Female
• Humans
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Neoadjuvant Therapy
• Neoplasm Recurrence, Local (drug therapy)
• Precision Medicine
• Prospective Studies