5. Tyverb ® (lapatinib): Mode of Action TYV/SLK/08/39072/1 Date of preparation: Nov 2008 Prescribing information can be found at the end of the full slide set
6. Tyverb is an oral, small-molecule, dual-targeted agent
7.
8. Tyverb ® (lapatinib): EGF100151 Study (Pivotal Registration Study) TYV/SLK/08/39072/1 Date of preparation: Nov 2008 Prescribing information can be found at the end of the full slide set
9. EGF100151 study design 1,2 Treatment continued until progression or unacceptable toxicity Patients with ErbB2-positive locally advanced or metastatic breast cancer that progressed after prior anthracycline, taxane and trastuzumab (N=399 ) RANDOMISATION 1. Cameron D et al. Breast Cancer Res Treat 2008 ; 2. Geyer GE et al. N Engl J Med 2006 Tyverb 1250 mg po od continuously + capecitabine 2000 mg/m 2 /d po days 1-14 q 3 wk Capecitabine 2500 mg/m 2 /day po days 1-14 q 3 wk po = oral; od = once daily; q 3 wk = once every 3 weeks
10.
11.
12.
13. EGF100151: prior therapy Cameron D et al. Breast Cancer Res Treat 2008 Tyverb + capecitabine (N=198) Capecitabine (N=201) Anthracyclines 194 (98) 199 (>99) Taxanes 198 (100) 199 (>99) Trastuzumab Metastatic Adjuvant Neoadjuvant 196 (99) 187 (95) 9 (5) 0 197 (98) 189 (94) 7 (4) 1 (<1) Median duration of trastuzumab, weeks (range) 44 (3-296) 45 (0-329) Time from discontinuation of trastuzumab to randomisation – no. < 4 weeks 4 - 8 weeks > 8 weeks Missing 196 55 (28) 62 (32) 79 (40) 0 197 52 (27) 65 (33) 77 (39) 3 (2)
15. EGF100151: key efficacy results 1 a Primary endpoint of the study 1 ; CI = confidence interval; TTP = time to progression; ORR = overall response rate (PR or CR); CR = complete response; PR = partial response Investigator assessment 2,3 Independent assessment 1 1. Cameron D et al. Breast Cancer Res Treat 2008; 2. Tyverb Summary of Product Characteristics; 3. GSK data on file (TYV/DOF/08/34764/1) Outcome Tyverb + capecitabine (N=198) Capecitabine (N=201) Hazard ratio (95% CI) Odds ratio (95% CI) p - value Median TTP [weeks (months)] a 27.1 (6.2) 18.6 (4.3) 0.57 (0.43, 0.77) – 0.00013 ORR (%) 23.7 13.9 – 1.9 (1.1, 3.4) 0.017 Outcome Tyverb + capecitabine (N=198) Capecitabine (N=201) Hazard ratio (95% CI) Odds ratio (95% CI) p - value Median TTP [weeks (months)] 23.9 (5.5) 18.3 (4.2) 0.72 (0.56, 0.92) – 0.008 ORR (%) 31.8 17.4 - 2.2 (1.3, 3.6) 0.002
16. EGF100151: overall survival by independent assessment 1. Cameron D et al. Breast Cancer Res Treat 2008 ; 2. Tyverb Summary of Product Characteristics September 2007 cut-off – after cross-over 2 April 2006 cut-off – before cross-over 1 Tyverb + capecitabine Capecitabine No. of patients 198 201 Median overall survival (weeks [months]) 67.7 (15.6) 66.6 (15.4) Hazard ratio (95% CI) 0.78 (0.55, 1.12) p-value 0.177 Tyverb + capecitabine Capecitabine No. of patients 207 201 Median overall survival (weeks [months]) 74.0 (17.1) 65.9 (15.2) Hazard ratio (95% CI) 0.9 (0.71, 1.12) p-value 0.3
17. EGF100151: effect of interval from last administration of trastuzumab to randomization on TTP Cameron D et al. Breast Cancer Res Treat 2008 Interval between last trastuzumab dose and randomization Tyverb + capecitabine Capecitabine alone Hazard ratio (95% CI) P value No. of pts Median TTP, wk No. of pts Median TTP, wk < 8 weeks 117 27.1 117 18.6 0.59 (0.40, 0.86) 0.004 > 8 weeks 79 26.1 77 14.6 0.56 (0.35, 0.91) 0.012
26. Tyverb ® (lapatinib): Practical considerations TYV/SLK/08/37076/1 Date of preparation: Nov 2008 Prescribing information can be found at the end of the full slide set
27. Tyverb ® (lapatinib): Dosage and administration TYV/SLK/08/39072/1 Date of preparation: Nov 2008 Prescribing information can be found at the end of the full slide set
32. Tyverb ® (lapatinib): Information for patients Practical advice on administering/dosing TYV/SLK/08/39072/1 Date of preparation: Nov 2008 Prescribing information can be found at the end of the full slide set