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

• Published in: ESMO open Vol. 7; no. 6; p. 100637
• Main Authors: Pixberg, C., Zapatka, M., Hlevnjak, M., Benedetto, S., Suppelna, J.P., Heil, J., Smetanay, K., Michel, L., Fremd, C., Körber, V., Rübsam, M., Buschhorn, L., Heublein, S., Schäfgen, B., Golatta, M., Gomez, C., von Au, A., Wallwiener, M., Wolf, S., Dikow, N., Schaaf, C., Gutjahr, E., Allgäuer, M., Stenzinger, A., Pfütze, K., Kirsten, R., Hübschmann, D., Sinn, H.-P., Jäger, D., Trumpp, A., Schlenk, R., Höfer, T., Thewes, V., Schneeweiss, A., Lichter, P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2022; Elsevier
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; curative precision oncology; early breast cancer; Female; Humans; molecularly targeted therapy; Neoadjuvant Therapy; Neoplasm Recurrence, Local - drug therapy; Original Research; Precision Medicine; prospective precision oncology trial; Prospective Studies; tumor evolution; early breast cancer; prospective precision oncology trial; tumor evolution; curative precision oncology; molecularly targeted therapy
• DOI: 10.1016/j.esmoop.2022.100637
• EISSN: 2059-7029

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.
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.
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.
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.
•The COGNITION molecular profiling diagnostic study has been recruiting in Heidelberg since April 2019 (pilot phase).•Evidence-based alterations in early breast cancer potentially increase cure rates by targeted post-neoadjuvant treatment.•Mutational profiles/signatures remain mostly stable, suggesting restricted selective pressure during neoadjuvant treatment.•COGNITION as the basis to develop the multiarm interventional phase II precision oncology therapy trial COGNITION-GUIDE.•COGNITION is one of the first initiatives in the early setting to potentially impact cure rates by molecular-guided therapies.