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维持治疗的分子靶标作用-课件(PPT·精·选).ppt


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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

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  • 时间2015-12-10