泰立沙(Tykerb)拉帕替尼(lapatinib)相关指南、规范与共识、关键临床研究回顾

1、TykerbTyrosine+kinase+erbB1&B2HER1/EGFRerbB1HER2/neuerbB2HER3erbB3HER4erbB4Tyrosine kinase指南、规范与共识Tykerb (lapatinib)+ capecitabine (2nd line)+ trastuzumab (2nd line)HER2阳性晚期/复发转移性乳腺癌，曲妥珠单抗治疗疾病进展后CACA, CBCS, 2011Tykerb (lapatinib)+ capecitabine (2nd line)+ trastuzumab (2nd line)HER2阳性乳腺癌曲妥珠单抗治疗出现疾病进展

2、后CACA, CBCS, 2012Tykerb (lapatinib)+ trastuzumab (2nd line)Systemic Treatment of Recurrent or Stage IV DiseaseER and PR Negative; or ER and/or PR Positive and Endocrine Refractory; and HER2 PositiveNCCN V2.2013Tykerb (lapatinib)+ capecitabine (2nd line)+ trastuzumab (2nd line)Chemotherapy Regimens f

3、or Recurrent or Metastatic Breast CancerTrastuzumab-Exposed HER2-Positive DiseaseNCCN V2.2013Tykerb (lapatinib)+ capecitabine (2nd line)+ letrozole (postmenopause)+ trastuzumab (2nd line)Besides T-DM1Other Regimens for Trastuzumab Exposed HER-Positive DiseaseNCCN V2.2013Tykerb (lapatinib)+ trastuzum

4、ab (neoadjuvant)Preoperative Chemotherapy for Large Tumors (Clinical stage IIA and IIB tumors and T3N1M0)NCCN V2.2013Tykerb (lapatinib)+ capecitabine (2nd line)+ letrozole (postmenopause)FDATykerb+summary泰立沙希罗达赫赛汀来曲唑指南推荐官方批准可以口服无细胞毒一线治疗新辅助绝经后二线治疗绝经后关键临床研究回顾TYKERB, a kinase inhibitor, is indicated in

5、 combination with: Capecitabine, for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab.FDA/SFDATykerb+capecitabine (2nd line)Lapatinib plus capecitabine for HER2-

6、positive advanced breast cancer.N Engl J Med. 2006;355(26):2733-2743.Tykerb+capecitabine (2nd line)Lapatinib plus capecitabine for HER2-positive advanced breast cancer.N Engl J Med. 2006;355(26):2733-2743.Tykerb+capecitabine (2nd line)Tykerb+capecitabine (2nd line)A phase III randomized comparison o

7、f lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumabBreast Cancer Res Treat. 2008;112(3):533-543.Tykerb+capecitabine (2nd line)HR=0.57(95%CI:0.43-0.77)P=0.00013mTTP延长1.9个月A phase III randomized comparison of lapatinib plus ca

8、pecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumabBreast Cancer Res Treat. 2008;112(3):533-543.Tykerb+capecitabine (2nd line)A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced bre

9、ast cancer that has progressed on trastuzumabBreast Cancer Res Treat. 2008;112(3):533-543.Tykerb+capecitabine (2nd line)A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab.Breast Cancer Res

10、 Treat. 2008;112(3):533-543.Tykerb+trastuzumab (2nd line)A randomized study of lapatinib alone or in combination with trastuzumab in heavily pretreated HER2+ metastatic breast cancer progressing on trastuzumab therapy. J Clin Oncol. 2008;26(15S):A1015.Tykerb+trastuzumab (2nd line)HR=0.77(95%CI:0.6-1

11、.0)P=0.029mPFS延长3.6个月12.08.4024681012mPFS (weeks)Tykerb+trastuzumabTykerbTykerb+trastuzumab (2nd line)A randomized study of lapatinib alone or in combination with trastuzumab in heavily pretreated HER2+ metastatic breast cancer progressing on trastuzumab therapy. J Clin Oncol. 2008;26(15S):A1015.HR=

12、2.1(95%CI:1.1-4.2)P=0.020CBR提高1.9倍25.213.2051015202530CBR (%)Tykerb+trastuzumabTykerbRandomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2 -positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010;28(7):1124-1130.Tykerb+trastuzumab (2nd line)

13、HR=0.73(95%CI:0.57-0.93)P=0.008mPFS延长3.9个月Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2 -positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010;28(7):1124-1130.Tykerb+trastuzumab (2nd line)HR=0.72(95%CI:0.57-0.93)P=0.008mPFS延长3.9个月1

14、2.08.1024681012mPFS (weeks)Tykerb+trastuzumabTykerbRandomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2 -positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010;28(7):1124-1130.Tykerb+trastuzumab (2nd line)HR=2.2(95%CI:1.2-4.5)P=0.01CBR提高1.

15、99倍24.712.40510152025CBR (%)Tykerb+trastuzumabTykerbTykerb+trastuzumab (neoadjuvant)Tykerb+trastuzumab (neoadjuvant)Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial.Lancet. 2012;379(9816):633-640.Tykerb+trastuzumab (neo

16、adjuvant)Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial.Lancet. 2012;379(9816):633-640.Tykerb+trastuzumab (neoadjuvant)Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-la

17、bel, multicentre, phase 3 trial.Lancet. 2012;379(9816):633-640.TYKERB, a kinase inhibitor, is indicated in combination with: letrozole for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer that over expresses the HER2 receptor for whom hormonal therapy is

18、indicated.FDATykerb+letrozole (postmenopause)Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for post- menopausal hormone receptor-positive metastatic breast cancerJ Clin Oncol. 2009;27(33):5538-5546.Tykerb+letrozole (postmenopause)Lapatinib combined with letrozo

19、le versus letrozole and placebo as first-line therapy for post- menopausal hormone receptor-positive metastatic breast cancerJ Clin Oncol. 2009;27(33):5538-5546.Tykerb+letrozole (postmenopause)P=0.019mPFS延长5.2个月Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for

20、post- menopausal hormone receptor-positive metastatic breast cancerJ Clin Oncol. 2009;27(33):5538-5546.Tykerb+letrozole (postmenopause)P=0.021ORR提高1.87倍28.015.0051015202530ORR (%)Tykerb+LetrozoleLetrozoleLapatinib combined with letrozole versus letrozole and placebo as first-line therapy for post- m

21、enopausal hormone receptor-positive metastatic breast cancerJ Clin Oncol. 2009;27(33):5538-5546.Tykerb+letrozole (postmenopause)P=0.003CBR提高1.66倍48.029.005101520253035404550CBR (%)Tykerb+LetrozoleLetrozoleLapatinib combined with letrozole versus letrozole and placebo as first-line therapy for post-

22、menopausal hormone receptor-positive metastatic breast cancerJ Clin Oncol. 2009;27(33):5538-5546.Tykerb+letrozole (postmenopause)To the best of our knowledge, this is the first demonstration of a statistically significant improve -ment in OS for HER2-targeted therapy combined with paclitaxel in the treatment of this disease. Prior pivotal work in the trastuzumab combined with paclitaxel-treated cohorts was not powered to demonstrate statistically significant results.Tykerb+paclitaxel (1st line)J Clin Oncol. 2013 Mar 18. Epub ahead of print中位总生存期延长7.3个月Tykerb+paclitaxel (1st line