In early breast cancer (eBC), pathological complete response (pCR) after neoadjuvant therapy acts as surrogate marker for metastasis and overall survival. Therapy intensification by adding an adjuvant therapy line (post-neoadjuvant treatment) substantially lowers the risk of relapse in high-risk breast cancer patients with residual disease after neoadjuvant treatment (non-pCR). While this approach was exemplified in two phase III trials without biomarker-stratification (CREATE-X, KATHERINE), even higher efficiency might be achieved by individualized genomic-guided post-neoadjuvant therapies.
Within the seven-arm umbrella phase-II clinical trial COGNITION-GUIDE, we aim to deliver molecularly-tailored cancer care by implementing an additional response- and genomics-guided post-neoadjuvant therapy after finishing the guideline-compliant post-neoadjuvant treatment in high-risk breast cancer patients with residual cancer burden after neoadjuvant therapy to reduce the substantial risk of local and distant relapse.
The trial evaluates not a single drug but rather a general strategy of precision oncology in the curative setting and provides the basis for future confirmatory biomarker-driven trials.
Allocation to the therapy-arms is conducted by in depth molecular characterization of tumors within the COGNITION registry program.
The study aims to show an overall benefit of the precision medicine approach in high-risk eBC patients and to allow for secondary exploratory evaluation of each study-arm.
The primary endpoint of the study is invasive Disease-Free Survival (IDFS) after 4 years measured from surgery to local or distant relapse or death. The sample size of the entire trial is 240 eligible patients.
Provision of written informed consent
Female and male patients with non-metastatic early (stage I-III) breast cancer aged ≥ 18 years
Conducted neoadjuvant chemotherapy and surgery as well as conducted standard post-neoadjuvant treatment +/- radiotherapy (standard according to German guidelines except Abemaciclib and Olaparib)
For patients with initially hormone receptor positive and HER2-negative breast cancer: Non-pCR and CPS-EG score
Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1 grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥ 5 year
Concurrent severe, uncontrolled systemic disease that would place patient at undue risk or interfere with planned treatment
Concurrent participation or previous treatment within 30 days in another interventional clinical trial
Persistent toxicity (≥ Grade 2 according to NCI CTCAE v5.0 caused by previous cancer therapy, excluding alopecia
Parallel
Atezolizumab 1200 mg in 20 ML Injection
DrugArm 1
Inavolisib
DrugArm 2
Ipatasertib
DrugArm 3
Olaparib
DrugArm 4
Sacituzumab govitecan
DrugArm 5
Trastuzumab/pertuzumab
DrugArm 6
7
Treatment groupsSee each treatment group below.
Invasive Disease-free Survival (IDFS) as defined by Hudis et al in the entire study population four years after surgery
Primary objective is to improve clinical outcome in early high-risk breast cancer by biomarker-guided post-neoadjuvant therapy (systemic treatment in the adjuvant setting following neoadjuvant therapy, surgery and post-neoadjuvant standard therapy)
Invasive Disease-free Survival (IDFS) as defined by Hudis et al
in each study arm separately
Distant Disease-free Survival (DDFS) as defined by Hudis et al
in each study arm separately and overall
Overall Survival
in each study arm separately and overall
Incidence of Treatment-Emergent Adverse Events (safety and tolerability)
in each study arm separately and overall
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