Philip C. Mack, PhD Associate Adjunct Professor UC Davis Cancer Center How do we perform more effective biomarker testing for matching NSCLC patients with optimal therapy for maintenance of disease remission and after relapsed NSCLC? A patient has benefited from treatment (tumor response or durable stable disease) How can we use biomarkers to help: 1) Maintain a responding patient in a disease control state? 2) Restore a relapsing patient to a disease control state? What biologic information is available? Baseline specimens Acquired prior to previous interventions Diagnostic FFPE specimen? Biomarker info obtained? Baseline blood draw? Post-progression specimens Acquired upon progression following meaningful benefit Second biopsy? Serial blood draws? Erlotinib Pemetrexed
Bevacizumab Docetaxel Gemcitabine Maintenance Therapy Options Maintenance Therapy Options and Associated Biomarkers Erlotinib – EGFR mutations predict response Evidence: High, well accepted, standard-of-care Pemetrexed – High TS predict resistance Evidence: Strong, requires additional validation over histology
Bevacizumab – No accepted markers for benefit Conjecture: Possibility of markers of acquired resistance? Docetaxel – Beta tubulin III mutations/expression levels Evidence: Weak, requires extensive further investigation Gemcitabine – High RRM1 levels predict resistance Evidence: Intriguing but controversial Biomarker strategies for “Continuous” maintenance therapy . pemetrexed maintenance in platinum + pem-treated patient with CR, PR or SD No biomarkers currently applicable Biomarkers should be used to aid front-line decision-making ess of front-line therapy is chief indicator for utility of continuous maintenance strategies Current research efforts focused on identification of emergent resistance markers Biomarker strategies for “Switch” maintenance therapy . erlotinib maintenance in carbo/pac-treated patient with CR, PR or SD Established biomarkers will be rel