CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016 Phase III MF07-01 Trial: Impact of Initial Local Resection on Stage IV Breast Cancer Survival *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.

Initial Local Resection of Stage IV Breast Cancer (MF07-01): Background  Systemic therapy is standard treatment approach for stage IV breast cancer  Meta-analyses suggest primary tumor resection may improve survival in stage IV breast cancer [1,2]  In select pts without disease progression on initial systemic therapy, subsequent surgery on primary an option  MF07-01 trial compared local regional surgery followed by systemic therapy vs systemic therapy with local therapy for localized progression in treatment- naive pts with stage IV breast cancer [3] 1. Harris E, et al. Ann Surg Oncol. 2013;20: Petrelli F, et al. Med Oncol. 2012;29: Soran A, et al. ASCO Abstract Slide credit: clinicaloptions.comclinicaloptions.com

MF07-01: Study Design  Multicenter phase III trial  Primary endpoint: OS  Secondary endpoints: morbidity and mortality, locoregional progression/relapse, QoL Treatment-naive pts with de novo stage IV breast cancer amenable for complete resection (N = 274) Local Resection of Breast ± Axilla (n = 138) Systemic Therapy (n = 136) Slide credit: clinicaloptions.comclinicaloptions.com Soran A, et al. ASCO Abstract Local Therapy for Local Progression Systemic Therapy

MF07-01: Additional Methods  BCS or mastectomy at preference of treating physician and pt –Must achieve free surgical margins –Whole-breast radiation therapy for all BCS; for mastectomy, based on institutional practice –Axillary clearance in pts with proven metastases  SoC systemic therapy administered immediately after randomization (systemic therapy arm) or after primary resection (surgery arm)  Metastatic site biopsy, treatment at discretion of treating physician Soran A, et al. ASCO Abstract Slide credit: clinicaloptions.comclinicaloptions.com

MF07-01: Pt Characteristics CharacteristicLocal Surgery (n = 138) Systemic Therapy (n = 136) Mean age, yrs ± SD51.8 ± ± 13.6 Tumor size T1/T2/T3/T4, %8.7/52.2/21.7/ /42.7/22.1/27.2 Receptor status, %  ER/PR+  HER2+  Triple negative Metastasis site, %  Bone only  Bone + others  Others (no bone)  Solitary bone  Multiple bone  Solitary pulmonary or liver  Multiple pulmonary or liver Slide credit: clinicaloptions.comclinicaloptions.com Soran A, et al. ASCO Abstract 1005.

MF07-01: Overall Survival  Surgery improved median survival by 9 mos SurvivalLocal Surgery (n = 138) Systemic Therapy (n = 136) HR (95% CI)P Value 3-yr survival, % yr survival, % Median OS, mos ( ).005 Slide credit: clinicaloptions.comclinicaloptions.com Soran A, et al. ASCO Abstract 1005.

MF07-01: OS by Pt Subgroups  Locoregional progression/relapse: surgery, 1% (n = 2); systemic therapy, 11% (n = 15); P = Yr Survival, %Median OS, Mos SubgroupSurgerySTPSurgerySTP ER/PR+ (n = 218) HER2/neu- (n = 189) < 55 yrs of age (n = 159) Bone only metastasis (n = 126) Solitary bone metastasis (n = 53) Multiple pulmonary/liver metastases (n = 28) 31*67* No locoregional progression/relapse (n = 257) Slide credit: clinicaloptions.comclinicaloptions.com Soran A, et al. ASCO Abstract *3-yr survival.

MF07-01: Conclusions  3-yr survival similar with or without primary breast tumor resection  However, with longer follow-up, there was significant improvement in 5-yr and median OS in surgery arm vs systemic therapy alone –Significant survival benefit with initial surgery seen in pt subgroups: ER/PR+, HER2/neu-, solitary bone metastasis, younger than 55 yrs of age –Pts with multiple liver/pulmonary metastases experienced worse OS with initial surgery  Incidence of locoregional progression 11-fold higher in initial systemic therapy group Slide credit: clinicaloptions.comclinicaloptions.com Soran A, et al. ASCO Abstract 1005.

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