1. CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016 KRISTINE: Neoadjuvant T-DM1 + Pertuzumab vs Chemotherapy With Trastuzumab + Pertuzumab in HER2+ EBC *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

2. KRISTINE: Neoadjuvant T-DM1 + Pertuzumab in HER2+ EBC  T-DM1: antibody–drug conjugate –Currently approved as single-agent treatment for pts with HER2-positive MBC who previously received trastuzumab and a taxane, separately or in combination  T-DM1 has shown clinical activity in HER2+ EBC [1-3]  Phase III KRISTINE study is a comparison of neoadjuvant T-DM1 + pertuzumab vs TCHP in HER2+ early breast cancer [4] 1. Krop IE, et al. Lancet Oncol. 2014;15:689-699. 2. Verma S, et al. N Engl J Med. 2012;367:1783-1791. 3. Ellis PA, et al. ASCO 2015. Abstract 507. 4. Hurvitz SA, et al. ASCO 2016. Abstract 500. Slide credit: clinicaloptions.comclinicaloptions.com

3. KRISTINE: Study Design  Open-label phase III trial  Primary endpoint: pCR by local assessment in breast, lymph nodes (ypT0/is, ypN0)  Secondary endpoints: safety, BCS rate, PROs, EFS, iDFS, OS  Stratified by: local hormone receptor status, geographic location, stage Stage II-IIIC HER2+ EBC with tumor > 2 cm (N = 444) 12 cycles adjuvant HER2 therapy* T-DM1 + Pertuzumab (n = 223) Docetaxel + Carboplatin + Trastuzumab + Pertuzumab (n = 221) Slide credit: clinicaloptions.comclinicaloptions.com 6 cycles neoadjuvant therapy Hurvitz SA, et al. ASCO 2016. Abstract 500. T-DM1 + Pertuzumab Trastuzumab + Pertuzumab Surgery *Adjuvant therapy recommended for pts in T-DM1/pertuzumab group with residual disease in lymph nodes or breast (> 1 cm).

4. KRISTINE: Pt Characteristics Characteristic TCHP (n = 221) T-DM1 + P (n = 223) Median age, yrs (range)49 (22-79)50 (23-79) Region, %  North America  Western Europe  Other regions 24 38 24 38 Local ER/PR status, %  ER- and PR-  ER+ and/or PR+ 38 62 38 62 Stage at presentation, %  IIa-IIIa  IIIb-IIIc 83 17 83 17 Slide credit: clinicaloptions.comclinicaloptions.com Hurvitz SA, et al. ASCO 2016. Abstract 500.

5. KRISTINE: Clinical Response Outcome TCHP (n = 221) T-DM1 + P (n = 223) pCR (ypT0/is, ypN0), % 5644 Difference: -11.3 (95% CI: -20.5 to -2.0; P =.0155) pCR by receptor status, %  ER- and PR-  ER+ and/or PR+ 73 44 54 35 BCS rate, %  Actual  Conversion* 53 70 42 66 Slide credit: clinicaloptions.comclinicaloptions.com Hurvitz SA, et al. ASCO 2016. Abstract 500.  Longer maintenance of health-related QoL (HR: 0.60) and physical function (HR: 0.47) with T-DM1 + P vs TCHP *Pts originally needing mastectomy who became eligible for BCS after neoadjuvant therapy.

6. KRISTINE: Safety (Neoadjuvant Phase) Outcome, % TCHP (n = 219) T-DM1 + P (n = 223) Any AE98.688.3 Serious AE28.84.9 Grade ≥ 3 AE (> 5%)  Any  Neutropenia  Febrile neutropenia  Diarrhea  Anemia  Decreased neutrophil count 64.4 25.1 15.1 9.6 9.1 13.0 0.4 0 0.9 0 AE leading to discontinuation of any treatment component 8.73.1 LVEF < 50% and ≥ 10% points decrease from baseline 0.50.4 Slide credit: clinicaloptions.comclinicaloptions.com Hurvitz SA, et al. ASCO 2016. Abstract 500.

7. KRISTINE: Conclusions  Superior pCR rate with neoadjuvant TCHP compared with T-DM1 + P in early breast cancer –Same effect in hormone receptor status subgroup analysis  Rate BCS lower in T-DM1 + P arm  Favorable safety profile of T-DM1 + P with lower incidence of serious and grade ≥ 3 AEs  Longer health-related QoL and physical functioning with T-DM1 + P compared with TCHP  Investigators suggest chemotherapy with trastuzumab + pertuzumab remain neoadjuvant standard of care for HER2+ breast cancer Slide credit: clinicaloptions.comclinicaloptions.com Hurvitz SA, et al. ASCO 2016. Abstract 500.

8. Go Online for More CCO Coverage of ASCO 2016! Short slideset summaries of all the key data Additional CME-certified analyses with expert faculty commentary on all the key studies in: Breast, genitourinary, and lung cancers Hematologic malignancies Immunotherapy clinicaloptions.com/oncology