泰立沙(Tykerb)拉帕替尼(lapatinib)相關(guān)指南、規(guī)范與共識(shí)、關(guān)鍵臨床研究回顧

1、TykerbTyrosine+kinase+erbB1&B2HER1/EGFRerbB1HER2/neuerbB2HER3erbB3HER4erbB4Tyrosine kinase指南、規(guī)范與共識(shí)Tykerb (lapatinib)+ capecitabine (2nd line)+ trastuzumab (2nd line)HER2陽(yáng)性晚期/復(fù)發(fā)轉(zhuǎn)移性乳腺癌，曲妥珠單抗治療疾病進(jìn)展后CACA, CBCS, 2011Tykerb (lapatinib)+ capecitabine (2nd line)+ trastuzumab (2nd line)HER2陽(yáng)性乳腺癌曲妥珠單抗治療出現(xiàn)疾病進(jìn)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泰立沙希羅達(dá)赫賽汀來(lái)曲唑指南推薦官方批準(zhǔn)可以口服無(wú)細(xì)胞毒一線治療新輔助絕經(jīng)后二線治療絕經(jīng)后關(guān)鍵臨床研究回顧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延長(zhǎng)1.9個(gè)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延長(zhǎng)3.6個(gè)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延長(zhǎng)3.9個(gè)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延長(zhǎng)3.9個(gè)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延長(zhǎng)5.2個(gè)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中位總生存期延長(zhǎng)7.3個(gè)月Tykerb+paclitaxel (1st line