乳腺癌分子靶向治疗.ppt

曲妥珠单抗新辅助治疗 MDAC、 NOAH、 GeparQuattro等临床研究 曲妥珠单抗联合化疗的新辅助治疗与仅用化疗的新辅助治疗比较，对HER2阳性的乳腺癌患者有较高的病理完全缓解率(pCR) Buzdar AU et al. Clin Cancer Res 2007; 13: 228-233. Baselga J et al. EJC Suppl 2007; 5: 193, abs #O2030. Gianni L et al. J Clin Oncol (Meeting Abstracts) 2007; 25: 10s, abs 532. Untch M et al. EJC Suppl 2008; 6: 47, abs 1LB. Phase III randomized, open-label neoadjuvant study Primary endpoint: pathologic CR NeoALLTO *Trastuzumab dose: 4 mg/kg IV loading dose, then 2 mg/kg IV/wk. Trastuzumab* (n = 149) Wk 6 Patients with operatable, HER2-positive invasive breast cancer (N = 455) Lapatinib 1500 mg/day (n = 154) Stratified by tumor size (≤ 5 vs 5 cm), ER/PgR status, N status (0-1 vs ≥ 2), conservative surgery (yes/no) Adjuvant FEC followed by same biologic regimen as induction for 34 wks Wk 18 Trastuzumab* Lapatinib 1000 mg/day + Trastuzumab* (n = 152) Surgery Paclitaxel 80 mg/m2/wk Lapatinib 750 mg/day Paclitaxel 80 mg/m2/wk Paclitaxel 80 mg/m2/wk Baselga J, et al. SABCS 2010. Abstract S3-3. Lapatinib + Trastuzumab NeoALLTO Primary Endpoint: Pathologic Complete Response Parameter, % Lapatinib(n = 154) Trastuzumab(n = 149) P Value Lapatinib vs Trastuzumab Lapatinib + Trastuzumab(n = 152) P Value Trastuzumab vs Lapatinib + Trastuzumab PCR overall 24.7 29.5 .34 51.3 .0001 Total PCR* 20.0 (n = 150) 27.6 (n = 145) .13 46.9 (n = 145) .001 PCR by hormone receptor status Positive 16.2 (n = 80) 22.7 (n = 75) .24 41.6 (n = 77) .03 Negative 33.8 (n = 74) 36.5 (n = 74) .75 61.3 (n = 75) .005 *Excludes 15 patients with nonevaluable nodal status. Baselga J, et al. SABCS 2010. Abstract S3-3. NeoALLTO: Adverse Events and Discontinuations Grade ≥ 3 Adverse Event, % Lapatinib(n = 154) Trastuzumab(n = 149) Lapatinib + Trastuzumab(n = 152) Diarrhea 23 2 21 Neutropenia 16 3 9 Hepatotoxicity 13 1 9 Skin disorders 7 3 7 Discontinued therapy 34 8 39 Baselga J, et al. SABCS 2010. Abstract S3-3. NeoALLTO In women with HER2-positive primary breast cancer, neoadjuvant lap