1. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer Slideset on: Piccart-Gebhart M, Procter M, Leyland- Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659-1672.

2. clinicaloptions.com/onco Oncology Journal Options Piccart-Gebhart M, et al. N Engl J Med. 2005;353:1659-1672. Background and Rationale  HER2 protein overexpression and/or HER2 gene amplification –Seen in 15%-20% of women with breast cancer –Linked to rapid tumor growth  Trastuzumab effective in women with metastatic HER2-positive breast cancer –This monoclonal antibody targets the extracellular domain of the HER2 protein –Acts as HER2 receptor antagonist

3. clinicaloptions.com/onco Oncology Journal Options Piccart-Gebhart M, et al. N Engl J Med. 2005;353:1659-1672. Baseline Characteristics Characteristic 1 Yr Trastuzumab, n (%) (n = 1694) Observation, n (%) (n = 1693) Nodes Negative 1-3 positive  4 positive 543 (32.1) 482 (28.5) 480 (28.3) 557 (32.9) 490 (28.9) 473 (27.9) Hormone receptor ER negative/PR negative ER negative/PR positive ER positive/PR positive ER positive/PR negative 798 (47.1) 88 (5.2) 526 (31.1) 210 (12.4) 817 (48.3) 85 (5.0) 459 (27.1) 246 (14.5) Tumor grade 3 (poorly differentiated) 2 (moderately differentiated) 1 (well differentiated) 1015 (59.9) 546 (32.2) 45 (2.7) 1012 (59.8) 554 (32.7) 42 (2.5) Chemotherapy No anthracyclines Anthracyclines, no taxanes Anthracyclines + taxanes 102 (6.0) 1151 (67.9) 440 (26.0) 104 (6.1) 1156 (68.3) 433 (25.6) ER, estrogen receptor; PR, progesterone receptor.

4. clinicaloptions.com/onco Oncology Journal Options Piccart-Gebhart M, et al. N Engl J Med. 2005;353:1659-1672. Summary of Study Design Patients with HER2-positive breast cancer treated with surgery, chemotherapy ± radiation Trastuzumab Initial dose, 8 mg/kg IV, then 6 mg/kg every 3 weeks for 1 year (n = 1694) Observation (n = 1693) Interim analysis † 1:1 randomization* *Randomization  7 weeks from first day of last chemotherapy cycle or  6 weeks from end of surgery or radiation, whichever was later. † Performed after 475 events were reported. Third arm of trastuzumab for 2 years (n = 1694) not reported as part of this interim analysis.

5. clinicaloptions.com/onco Oncology Journal Options Piccart-Gebhart M, et al. N Engl J Med. 2005;353:1659-1672. Main Findings Study Endpoint 1 Yr Trastuzumab* (n = 1694) Observation* (n = 1693) Hazard RatioP Value 2-year disease-free survival85.8 (83-89)77.4 (74-81)0.54 (0.43-0.67)<.0001 2-year freedom from distant recurrence 90.6 (88-93)82.8 (80-86)0.49 (0.38-0.63)<.0001 2-year overall survival96.0 (94-98)95.1 (93-97)0.76 (0.47-1.23).26 *% patients (95% confidence interval).

6. clinicaloptions.com/onco Oncology Journal Options Piccart-Gebhart M, et al. N Engl J Med. 2005;353:1659-1672. Key Conclusions  Adjuvant trastuzumab effective for HER2-positive breast cancer patients after primary therapy –Disease recurrence decreased, especially distant recurrence –No significant difference in overall survival  Low rate of cardiac toxicity, but significantly greater than in control group  1-year course of adjuvant trastuzumab recommended as standard treatment