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DOI: 10.1055/a-2557-1876
COGNITION-GUIDE – Genomics-Guided Targeted Post-Neoadjuvant Therapy in Patients with Early Breast Cancer: Study Design of a Multicenter, Open-Label, Umbrella Phase II Study
COGNITION-GUIDE – Molekulare Diagnostik zur Stratifizierung der post-neoadjuvanten Therapie bei Patientinnen mit Brustkrebs im Frühstadium: Studiendesign einer multizentrischen Open-Label-Umbrella-Phase-II-Studie
Abstract
Background
As part of the COGNITION diagnostic registry program, residual tumor material after neoadjuvant therapy (NAT) of patients with early breast cancer (eBC), who are still at high-risk for relapse after NAT, is analyzed by next generation sequencing to identify biomarkers and actionable alterations. This strategy aims to stratify patients for subsequent genomics-guided therapies to reduce the significant risk of metastatic dissemination and hence to improve disease-free survival.
Patients and Methods
COGNITION-GUIDE is a multicenter umbrella phase-II-trial to translate molecular biomarker profiles generated in the COGNITION platform into six molecular-guided post-neoadjuvant therapeutic options in addition to standard-of-care treatment. Patients can be allocated to
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immune checkpoint inhibition (PD-L1-antibody),
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PI3K inhibition,
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AKT inhibition,
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PARP inhibition,
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anti-Trop-2 antibody-drug-conjugate,
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HER2 inhibition or, in case of missing biomarkers, to observation for 12 months.
The primary endpoint is invasive disease-free survival (IDFS) four years after surgery. Secondary endpoints include IDFS in each study arm separately, distant disease-free survival, overall survival and safety. 240 patients will be enrolled within four years.
Conclusions
The COGNITION-GUIDE trial, which was activated in June 2023 and will recruit in different centers in Germany, empowers a risk-adapted, biomarker-guided therapy escalation algorithm in eBC patients who are still at high risk of metastasis.
Zusammenfassung
Hintergrund
Im Rahmen der COGNITION-Diagnostik-Studie wird verbleibendes Tumorgewebe nach neoadjuvanter Therapie (NAT) von Patientinnen mit Brustkrebs im Frühstadium (eBC), die nach NAT ein erhöhtes Rückfallrisiko haben, mithilfe von Next Generation Sequencing analysiert, um Biomarker sowie aktionsfähige genomische Alterationen zu identifizieren. Das Ziel ist eine Stratifizierung der Patientinnen für nachfolgende genomikgeleitete Therapien, um das erhebliche Risiko einer metastatischen Disseminierung zu reduzieren und dadurch das krankheitsfreie Überleben zu verbessern.
Patientinnen und Methoden
COGNITION-GUIDE ist eine multizentrische, übergreifende Phase-II-Studie zur Umsetzung von molekularen Biomarkerprofilen, die mit der COGNITION-Plattform erstellt wurden, in 6 molekular geleitete post-neoadjuvante Therapieoptionen zusätzlich zur Standardbehandlung. Die Patientinnen werden einer Behandlung mit
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Immuncheckpoint-Inhibitor (PD-L1-Antikörper),
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PI3K-Inhibitor,
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AKT-Inhibitor,
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PARP-Inhibitor,
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Anti-Trop-2 Antikörper-Wirkstoff-Konjugat,
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HER2-Inhibitor oder, im Falle fehlender Biomarker, einer Beobachtung über 12 Monate hinweg zugeführt.
Der primäre Endpunkt der Studie ist das invasive krankheitsfreie Überleben (IDFS) 4 Jahre nach dem operativen Eingriff. Zu den sekundären Endpunkten gehören das IDFS für jeden Studienarm, das fernmetastasenfreie Überleben, das Gesamtüberleben und die Sicherheit. Über einen Zeitraum von 4 Jahren werden 240 Patientinnen in die Studie aufgenommen.
Schlussfolgerungen
Die im Juni 2023 aktivierte COGNITION-GUIDE-Studie wird bundesweit in verschiedenen Zentren Patientinnen rekrutieren. Die Studie soll die Grundlage für einen risikoadaptierten, biomarkergeleiteten Algorithmus zur Therapieeskalation bei eBC-Patientinnen mit einem hohen Metastasenrisiko schaffen.
Schlüsselwörter
Präzisionsonkologie - Brustkrebs im Frühstadium - laufende klinische Studie - zielgerichtete Therapie** Jan Philip Suppelna is now an employee of Sanofi-Aventis GmbH.
*** These authors contributed equally.
Supplementary Material
- Supporting Information
• Supplementary Table S1: CPS-EG-Score.
• Supplementary Table S2: Biomarker selection for each arm including most relevant evidence in literature.
Publication History
Received: 23 October 2024
Accepted after revision: 01 March 2025
Article published online:
10 April 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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