《EGFR靶向治疗癌症》PPT课件.ppt

Current status of EGFR-targeted cancer therapy,S, Surgery; RT, Radiotherapy; CT, Chemotherapy/hormone therapy EGFR, epidermal growth factor receptor,Pre- malignancy,Localized tumors,Locally/ regionally advanced disease,Advanced/ metastatic disease,S,RT,CT + RT,CT,EGFR-targeted therapy,Potential treatment options for EGFR-targeted therapies,The concept Targeted therapy for a broad range of common solid tumors (including lung, breast, prostate, colon, ovarian, and gastric) Clinical trials Proof of concept well-tolerated therapy tumor responses in several tumor types The potential Improved outcomes in the treatment of common solid tumors,From concept to clinical trials,Tumor response,mAbs,TKIs,mAbs, monoclonal antibodies; TKIs, tyrosine kinase inhibitors,Clinical development of anticancer agents,Typical cytotoxic OBD MTD,MTD,OBD,Toxicity,Antitumor effect,Effect,Target,Dose,OBD,MTD,Novel targeted agents OBD MTD,OBD, optimal biologic dose; MTD, maximum tolerated dose Rowinsky 2000,Dose,Effect,Target,Antitumor effect,Toxicity,Clinical development of EGFR-targeted therapies,Phase I trials failed to identify the MTD of cetuximab; the OBD was identified as the dose that saturated the antibody systemic clearance rate (200 mg/m2/week) Gefitinib (IRESSA) Phase I trials did identify the MTD (700-1000 mg/day), but also showed that the OBD was 250 mg/day, as confirmed in Phase II trials Phase I trials of erlotinib identified the MTD as 150 mg/day; this is the recommended dose,Baselga et al 2000; Baselga et al 2002; Herbst et al 2002; Nakagawa et al 2003; Ranson et al 2002; Fukuoka et al 2003; Kris et al 2003; Hidalgo et al 2001,Cetuximab: approved for the treatment of advanced colorectal cancer,Partial response rate, % Disease control rate, % Median TTP, months Median survival, months,Combination* (n=218) 22.9 55.5 4.1 8.6,Monotherapy (n=111) 10.8 32.4 1.5 6.9,p value 0.007 0.001 0.001 0.48,*Cetuximab in combination with irinotecan TTP, time to progression,Cunningham et al 2003,Gefitinib (250 mg/day): approved for the treatment of advanced NSCLC,Response rate, % Disease control rate, % Median survival, months 1-year survival, % Symptom improvement*, %,IDEAL 1 (n=103) 18.4 54.4 7.6 35 40.3,IDEAL 2 (n=102) 11.8 42.2 6.5 27 43.1,*Assessed in 67 symptomatic patients in IDEAL 1 and 102 symptomatic patients in IDEAL 2,Fukuoka et al 2003; Kris et al 2003,Erlotinib: awaiting approval for the treatment of advanced NSCLC,Perez-Soler et al 2003,Other EGFR-targeted therapies under clinical development,EMD72000,h-R3,ABX-EGF,PKI-1066,CI-1033,EKB-569,mAbs,TKIs,Summary of current EGFR-targeted treatment options,To date, two EGFR-targeted therapies have been approved for the treatment of patients with advanced or metastatic CRC (cetuximab) or NSCLC (gefitinib) Approval of erlotinib for the treatment of advanced NSCLC is expected i