WHEN BIOMARKERS EVOLVE FASTER THAN PICOS: EVIDENCE-BASED JCA MAPPING IN KRAS-MUTATED NON-SMALL CELL LUNG CANCER (NSCLC) USING REAL-SLR
Author(s)
Stacy Grieve, PhD1, Anna Forsythe, MBA, MSc, PharmD1, Stefan Walzer, MA, PhD2, Saro Sarkisian, MD3.
1Oncoscope, Miami, FL, USA, 2MArS Market Access & Pricing Strategy GmbH, Weil am Rhein, Germany, 3Frederick Health, Frederick, MD, USA.
1Oncoscope, Miami, FL, USA, 2MArS Market Access & Pricing Strategy GmbH, Weil am Rhein, Germany, 3Frederick Health, Frederick, MD, USA.
OBJECTIVES: Successful EU Joint Clinical Assessments (JCAs) depend on establishing the PICO framework (Population, Intervention, Comparator, Outcome) early and with transparent and evidence-based definitions. In advanced NSCLC, KRAS mutations occur in up to 30% of patients, and and emerging KRAS-targeted therapies are expanding beyond the currently approved KRAS G12C population. As treatment pathways, biomarkers, and comparator landscapes evolve, continuous evidence monitoring becomes increasingly important for JCA preparedness. We evaluated the use of a REAL-Time AI-Assisted Systematic Literature Review (REAL-SLR) to support evidence-based PICO mapping in KRAS-mutated NSCLC.
METHODS: A PRISMA-compliant, continuously updated REAL-SLR was conducted using the NSCLC database. Evidence from clinical trials, regulatory sources, clinical guidelines, and HTA documents was systematically identified and synthesized. Studies were mapped by population, intervention, comparator, outcomes, biomarker, line of therapy and subgroups. This continuously updated evidence base was used to map JCA-relevant PICOs.
RESULTS: As of June 17, 2026, the REAL-SLR identified 73 published studies in metastatic KRAS-mutated NSCLC, including 52 trials in the ≥2nd line setting. Evidence mapping established core JCA-relevant PICOs and identified multiple extended populations based on KRAS-mutation subtype, including G12C (n=18), non-G12C/D (n=7), and mixed populations (n=27). Additional stratification identified clinically relevant subgroups defined by brain metastases and co-mutations including TP53, STK11, LKB1, which may influence treatment effect and future JCA subgroup analyses. Intervention/comparator landscapes included KRAS-targeted therapies (n=28), antibody-drug conjugates (n=2), and emerging approaches including G12D-targeted therapies, non-covalent inhibitors, degraders, pan-KRAS inhibitors, or RAS (ON/OFF) inhibitors.
CONCLUSIONS: REAL-SLR-enabled continuous, evidence-based in KRAS-mutated NSCLC and identified evolving populations and comparator classes likely to influence future JCA scope. Living evidence approaches may improve transparency, reduce evidence-generation risk, support earlier identification of HTA-relevant subgroups and comparators, and enhance JCA preparedness in rapidly evolving oncology indications.
METHODS: A PRISMA-compliant, continuously updated REAL-SLR was conducted using the NSCLC database. Evidence from clinical trials, regulatory sources, clinical guidelines, and HTA documents was systematically identified and synthesized. Studies were mapped by population, intervention, comparator, outcomes, biomarker, line of therapy and subgroups. This continuously updated evidence base was used to map JCA-relevant PICOs.
RESULTS: As of June 17, 2026, the REAL-SLR identified 73 published studies in metastatic KRAS-mutated NSCLC, including 52 trials in the ≥2nd line setting. Evidence mapping established core JCA-relevant PICOs and identified multiple extended populations based on KRAS-mutation subtype, including G12C (n=18), non-G12C/D (n=7), and mixed populations (n=27). Additional stratification identified clinically relevant subgroups defined by brain metastases and co-mutations including TP53, STK11, LKB1, which may influence treatment effect and future JCA subgroup analyses. Intervention/comparator landscapes included KRAS-targeted therapies (n=28), antibody-drug conjugates (n=2), and emerging approaches including G12D-targeted therapies, non-covalent inhibitors, degraders, pan-KRAS inhibitors, or RAS (ON/OFF) inhibitors.
CONCLUSIONS: REAL-SLR-enabled continuous, evidence-based in KRAS-mutated NSCLC and identified evolving populations and comparator classes likely to influence future JCA scope. Living evidence approaches may improve transparency, reduce evidence-generation risk, support earlier identification of HTA-relevant subgroups and comparators, and enhance JCA preparedness in rapidly evolving oncology indications.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HTA93
Topic
Health Technology Assessment
Topic Subcategory
Systems & Structure
Disease
Oncology