Presentation (CTI)

OBJECTIVES: The EU Joint Clinical Assessment (JCA) requires early, transparent, and evidence-based definition of Population-Intervention-Comparator-Outcome (PICO) frameworks. In hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC), rapid therapeutic innovation following progression on CDK4/6 inhibitors, expanding treatment classes, and increasing reliance on subgroup analyses challenge traditional static systematic literature reviews (SLRs) for JCA planning. This paper presents a Real-Time AI-assisted Living SLR (REAL-SLR) approach for evidence-based JCA PICO mapping in HR+/HER2-mBC.
METHODS: A PRISMA-compliant REAL-SLR was conducted using protocol-driven searches updated continuously for metastatic breast cancer. Evidence from interventional clinical trials, regulatory sources, clinical guidelines, selected high-quality real-world evidence, and technology assessments was continuously identified, screened, and structured. For each eligible study, data were extracted on study design, population, intervention, comparator, endpoints, and reported subgroup analyses. This continuously updated evidence-base REAL-SLR was used to define both core and extended JCA PICOs without re-running searches, enabling dynamic refinement while preserving auditability and methodological consistency.
RESULTS: As of January 8, 2026, the REAL-SLR identified 144 published studies in HR+/HER2- mBC following progression on CDK4/6 inhibitor therapy, including 36 Phase 2 or Phase 3 randomized controlled trials, which defined the evidence-anchored core PICOs. Interventions/comparators across these studies included endocrine therapy (ET), targeted therapy with/without ET, chemotherapy, and antibody-drug conjugates. Extended PICOs were mapped using biomarker-defined subpopulations (PIK3CA/AKT1/PTEN alterations, HER2-low/ultra-low disease), subgroup evidence, including brain/bone/liver metastases, prior CDK4/6-inhibitor use (adjuvant vs metastatic), and prior treatment exposure patterns including concurrent vs sequential ET/CDK4/6-inhibitor therapy.
CONCLUSIONS: REAL-SLR-enabled PICO mapping anchors JCA scoping in the evolving metastatic breast cancer evidence landscape rather than a single trial design. By distinguishing evidence-anchored core PICOs based on interventions and sub-populations in published studies, this approach improves transparency, reduces rework, and enhances preparedness for JCA in complex and rapidly evolving oncology indications.