乳腺癌TKI治疗ppt课件.ppt

Sunitinib in Combination with Docetaxel vs. Docetaxel Alone for the First-line Treatment of Advanced Breast Cancer Endpoints and Statistical Hypothesis Primary endpoint: PFS Hypothesis: 50% increase in median PFS (from 6 to 9 months) in ITT population (independent central review), based on 285 events, power of 90%, alpha error 0.025, one sided log-rank test Secondary endpoints PFS (investigator assessment) ORR, duration of response OS Safety Median follow-up: 18.0 months (95% CI: 17.6?18.4) Fatalities Phase 3 Trial of Sunitinib in Combination with Capecitabine vs. Capecitabine in Previously Treated Advanced Breast Cancer 多靶点TKI治疗 * ORR: 1-sided P value = 0.490 * ORR: 1-sided P value = 0.189 * * * Overall Response in Patients with Measurable Disease (Investigator Assessment) Response parameter SU + CAP n=206 CAP n=201 Objective response rate,* % 95% exact CI 27 21?34 22 17?29 Complete response, % 0 1 Partial response,% 27 21 Stable disease, % 46 50 Stable disease ≥26 weeks, % 13 14 Median duration of response, months, 95% CI 5.7 4.3?6.9 7.6 6.5?9.9 *% CR + PR Conclusions The study did not meet its primary endpoint Sunitinib in combination with capecitabine did not improve efficacy compared with capecitabine alone The frequency of AEs was higher with sunitinib and capecitabine than with capecitabine alone Treatment discontinuations and dosing modifications occurred more frequently in the combination arm The sunitinib?capecitabine regimen evaluated in this study is not recommended for second- or third-line treatment of patients with ABC 拉帕替尼 Lapatinib oral tyrosine kinase inhibitor of ErbB1 and ErbB2 Blocks signaling through EGFR and HER2 homodimers and heterodimers May also prevent signaling between ErbB1/ErbB2 and other ErbB family members PTEN Lapatinib P13K pAkt Ras Raf pErk Shc Grb2 So8 Phospholipid cell membrane 到疾病进展时间（ITT Population） 70 20 40 60 80 0 100 10 20 30 40 50 60 0 Time (weeks) Patients Progression Free* (%) Lap + Cap Cap 病例数, n 160 161 Med