肺癌 Randomized Phase II trial of erlotinib (E) alone or in combination with carboplatin-paclitaxel (CP) in never or light former smokers with advanced lung adenocarcinoma CALGB 30406.ppt

Prospective Studies of Patients with EGFR mutations treated with EGFR TKIs Gefitinib is more effective than Chemotherapy in treatment naive EGFR mutant advanced NSCLC EGFR TKI Therapy in 2010 Efficacy (RR and PFS) greatest in EGFR mutant patients Single agent activity in EGFR mutants1,2 1st line response rate: 60%-80% 1st line progression free survival 10 – 14 months Gefitinib superior to 1st line chemotherapy1 Higher RR and longer PFS Better toxicity profile How to Improve Outcome of First Line EGFR TKI Therapy ? Add chemotherapy to EGFR inhibitors CALGB 30406 Use an alternative EGFR inhibitor BIBW2992 CALGB 30406 Study conduct Written 2004; activated 8/05; closed 4/09 Median follow-up: 30 months Events: PFS: 82%; OS: 58% 26 pts (14%) still receiving study therapy Tissue submission part of eligibility Routine genotyping not available in 2004 Prospective evaluation of EGFR mutations Primary Endpoint PFS in each arm Secondary Endpoints RR, PFS and OS in EGFR WT and EGFR mutant pts. CALGB 30406: Statistical Design Calculation based on PFS of chemotherapy alone arm in never smokers (TRIBUTE) Both arms: sample size driven by testing proportion of patients progression free at 18 weeks (4.1 mos) (p) with α=0.1 and β=0.1 Erlotinib alone arm: 80 pts. H0: p0.37 vs H1: p0.52; p=.37 ~ m PFS 2.9mos Erlotinib/carboplatin/paclitaxel: 100 pts. H0: p0.49 vs H1: p0.62; p=.49 ~ m PFS 4.0mos Patient Characteristics Treatment Duration Grade 3/4 Adverse Events How to Improve Outcome of First Line EGFR TKI Therapy ? Add chemotherapy to EGFR inhibitors CALGB 30406 No clear signal that adding chemotherapy to an EGFR TKI is any better than an EGFR TKI alone in EGFR mutant NSCLC Use an alternative EGFR inhibitor BIBW2992 PFS of first line EGFR mutant patients is similar to erlotinib but more toxic Clinical and Demographic Features of Patients with ALK-positive NSCLC N=82 Mean (range) age, years 51 (25–78) Gender, male/female 43/39 Performance status,* n (%) 0 24 (29) 1 44 (54) 2