Alessandra Curioni, University and Hospital Fribourg

💬 Biography
Alessandra Curioni-Fontecedro is the Head of Medical Oncology at the Hospital of Fribourg and Chair of Oncology at the University of Fribourg. She is the president of the Lung Cancer Group at the Swiss Cancer Institute and a member of the Council of the European School of Oncology (ESO). At ESMO, she is faculty member of the Investigational Immunotherapy Group. Prof Curioni-Fontecedro obtained her medical in Rome, Italy. She did a double MD at the Department of Molecular Biology of the University of Zurich and at the University Campus Bio-Medico in Rome. She was scientific physician at the Laboratory of Immuno-Oncology of the University Hospital in Zurich and at the laboratory of Experimental Immunology of the University of Zurich. Previously deputy director of the Lung Cancer Center at the University Hospital of Zurich, she is principal investigator locally, nationally and internationally of multiple trials in the field of thoracic oncology.

🎤 Presentation: KRAS mutated NSCLC
KRAS mutations occur in ~25–30% of lung adenocarcinoma. Subtypes: G12C (~35–45%), G12V (~18–21%), G12D (~14–18%—more in never-smokers).  Two covalent KRAS-G12C inhibitors have regulatory clearance after prior therapy for metastatic NSCLC: sotorasib (CodeBreaK program) and adagrasib (KRYSTAL-1; confirmatory KRYSTAL-12 met PFS). CodeBreaK 200 showed PFS benefit vs docetaxel; OS neutral. New G12C inhibitors (divarasib/GDC-6036, JDQ443, olomorasib) show promising activity and are in comparative and combo trials; pan-KRAS(ON) and non-G12C agents are emerging to address resistance and non-G12C subtypes. For early stages, multiple studies are exploring neoadjuvant G12C inhibitors (e.g., adagrasib; opnurasib).  On-target KRAS mutations and bypass via RTK/SHP2/SOS1–MAPK reactivation; hence the emphasis on SHP2/SOS1 combinations and next-gen/pan-KRAS agents.