Slamon D et al. SABCS 2009;Abstract 62.

Slides:

Advertisements

Similar presentations

San Antonio Breast Cancer Symposia Authors: Dr. Sunil Verma Date posted: January 6 th, 2008.

Advertisements

First Efficacy Results of a Randomized, Open- Label, Phase III Study of Adjuvant Doxorubicin Plus Cyclophosphamide, Followed by Docetaxel with or without.

Integration of Taxanes in the Management of Breast Cancer

516 (32723) Phase III trial comparing AC (x4)taxane (x4) with taxane (x8) as adjuvant therapy for node-positive breast cancer: Results of N-SAS-BC02.

Oncologic Drugs Advisory Committee

Chemotherapy Prolongs Survival for Isolated Local or Regional Recurrence of Breast Cancer: The CALOR Trial (Chemotherapy as Adjuvant for Locally Recurrent.

Obesity at Diagnosis Is Associated with Inferior Outcomes in Hormone Receptor Positive Breast Cancer 1 The Impact of Body Mass Index (BMI) on the Efficacy.

Integration of Capecitabine into Anthracycline- and Taxane-Based Adjuvant Therapy for Triple Negative Early Breast Cancer: Final Subgroup Analysis of the.

Updates from the San Antonio Breast Cancer Symposium 2013 HER2+ Breast Cancer Julie R. Gralow, M.D. Director and Jill Bennett Professor of Breast Medical.

Herceptin® (trastuzumab) in combination with chemotherapy: pivotal metastatic breast cancer survival data 1.

BCIRG006 - Randomized Phase III Trial Comparing AC-T vs AC-TH vs TCH in HER2 Positive Node Positive or High Risk Node Negative Breast Cancer Initial efficacy.

Clinical Relevance of HER2 Overexpression/Amplification in Patients with Small Tumor Size and Node-Negative Breast Cancer Curigliano G et al. J Clin Oncol.

A Meta Analysis of Risk of Cardiovascular Events in Patients with Metastatic Breast Cancer (MBC) Treated with Anti Vascular Endothelial Growth Factor (VEGF)

First Safety Data from a Randomized Phase III (CIBOMA/ /GEICAM ) Trial Assessing Adjuvant Capecitabine Maintenance Therapy After Standard.

HERA: KEY DESIGN ELEMENTS, RESULTS AND FUTURE PLANS NSABP 17 SEPTEMBER 2005 Brian Leyland-Jones Minda De Gunzberg Professor of Oncology, McGill University,

A randomized three-arm multi-centre comparison of: 1 year Herceptin®1 year Herceptin® 2 years Herceptin®2 years Herceptin® or no Herceptin®or no Herceptin®

NCCTG N9831 May 2005 Update Perez EA, Suman VJ, Davidson N, Martino S, Kaufman P, on Behalf of NCCTG, ECOG, SWOG, CALGB.

Van Cutsem E et al. ASCO 2009; Abstract LBA4509. (Oral Presentation)

Sgroi DC et al. Proc SABCS 2012;Abstract S1-9.

Should clinicians routinely recommend trastuzumab (Herceptin) as part of the adjuvant therapy for all patients with Her2 positive early breast cancer?

Herceptin ® : leading the way in metastatic breast cancer care Steffen Kahlert.

Assistant Professor of Medicine Dana-Farber Cancer Institute

The Use of Trastuzumab in the Elderly in the Adjuvant Setting and After Disease Progression in Patients with HER2-Positive Advanced Breast Cancer Dall.

Herceptin ® adjuvant therapy: “a triumphal narrative of translational research” Brian Leyland-Jones McGill University Department of Oncology Montreal,

Sunil Verma MD, MSEd, FRCPC Medical Oncologist

1Bachelot T et al. Proc SABCS 2010;Abstract S1-6.

Trastuzumab plus Adjuvant Chemotherapy for HER2-Positive Breast Cancer: Final Planned Joint Analysis of Overall Survival from NSABP B-31 and NCCTG N9831.

Final Analysis of Overall Survival for the Phase III CONFIRM Trial: Fulvestrant 500 mg versus 250 mg Di Leo A et al. Proc SABCS 2012;Abstract S1-4.

Lapatinib versus Trastuzumab in Combination with Neoadjuvant Anthracycline-Taxane-Based Chemotherapy: Primary Efficacy Endpoint Analysis of the GEPARQUINTO.

Cortés J et al. ASCO 2009; Abstract (Poster Discussion)

Baselga J et al. Proc SABCS 2010;Abstract S3-3.

Low Dose Decitabine Versus Best Supportive Care in Elderly Patients with Intermediate or High Risk MDS Not Eligible for Intensive Chemotherapy: Final Results.

HERA TRIAL: 2 Years versus 1 Year of Trastuzumab After Adjuvant Chemotherapy in Women with HER2-Positive Early Breast Cancer at 8 Years of Median Follow-Up.

Adjuvant therapy of HER2 positive early breast cancer The Evidences Antonio Frassoldati Oncologia Clinica - Ferrara.

A Phase III, Open-Label, Randomized, Multicenter Study of Eribulin Mesylate versus Capecitabine in Patients with Locally Advanced or Metastatic Breast.

Response-Guided Neoadjuvant Chemotherapy for Breast Cancer Gunter von Minckwitz, Jens Uwe Blohmer, Serban Dan Costa, Carsten Denkert, Holger Eidtmann Journal.

Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer Slideset on: Piccart-Gebhart M, Procter M, Leyland- Jones B, et al. Trastuzumab.

Results of a Phase 2, Multicenter, Single-Arm Study of Eribulin Mesylate as First-Line Therapy for Locally Recurrent or Metastatic HER2-Negative Breast.

Phase III Trial Comparing AC-T with AC-TH and with TCH in the Adjuvant Treatment of HER2 positive Early Breast Cancer Patients: First Interim Efficacy.

PHARE Trial Results of Subset Analysis Comparing 6 to 12 Months of Trastuzumab in Adjuvant Early Breast Cancer Pivot X et al. Proc SABCS 2012;Abstract.

Four-Year Follow-Up of Trastuzumab Plus Adjuvant Chemotherapy for Operable Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Joint Analysis.

CCO Independent Conference Coverage*: The 2015 Annual Meeting of the CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2015 San Antonio, Texas.

CCO Independent Conference Coverage

CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016 KRISTINE: Neoadjuvant T-DM1 + Pertuzumab vs Chemotherapy With Trastuzumab.

Mamounas EP et al. Proc SABCS 2012;Abstract S1-10.

Alessandra Gennari, MD PhD

TRAIN-2 (BOOG ): Phase III Trial of Neoadjuvant Chemotherapy ± Anthracyclines With Dual HER2 Blockade in HER2+ EBC CCO Independent Conference Highlights*

CCO Independent Conference Highlights

Gajria D et al. Proc SABCS 2010;Abstract P

Perez EA et al. SABCS 2009;Abstract 80.

Prognostic and Predictive Value of the 21-Gene Recurrence Score Assay in Postmenopausal Women with Node-Positive, Estrogen- Receptor-Positive Breast Cancer.

CREATE-X: Adjuvant Capecitabine in HER2-Negative Breast Cancer

Biologika bei onkologischen Erkrankungen älterer Menschen

Blackwell KL et al. SABCS 2009;Abstract 61

ASCO 2002 Advances in the Adjuvant Chemotherapy of Breast Cancer

Figure 1. Adjuvant trastuzumab study designs

Vahdat L et al. Proc SABCS 2012;Abstract P

Swain SM et al. Proc SABCS 2012;Abstract P

European Cooperative Trial in Operable Breast Cancer(ECTO): Improved freedom from progression from adding paclitaxel(T) to doxorubicin(A) followed by CMF.

Barrios C et al. SABCS 2009;Abstract 46.

Krop I et al. SABCS 2009;Abstract 5090.

Bergh J et al. SABCS 2009;Abstract 23.

Jones SE et al. SABCS 2009;Abstract 5082.

Untch M et al. Proc SABCS 2010;Abstract P

Reviewer: Dr. Sunil Verma Date posted: December 12th, 2011

Baselga J et al. SABCS 2009;Abstract 45.

Effect of Obesity on Prognosis after Early Breast Cancer

Martin M et al. Proc SABCS 2012;Abstract S1-7.

Badwe RA et al. SABCS 2009;Abstract 72.

Presentation transcript:

Slamon D et al. SABCS 2009;Abstract 62. BCIRG 006 Phase III Trial Comparing AC  T with AC  TH and with TCH in the Adjuvant Treatment of HER2-Amplified Early Breast Cancer Patients: Third Planned Efficacy Analysis Slamon D et al. SABCS 2009;Abstract 62.

Introduction Trastuzumab treatment is associated with cardiac dysfunction, especially in patients who have received anthracyclines. Pre-clinical data suggested that there is a synergy between trastuzumab and docetaxel/carboplatin that is not seen with anthracyclines. Current study objectives: Assess the efficacy, safety and cardiac safety of an anthracycline regimen compared to the same regimen with trastuzumab (H) versus a nonanthracycline regimen with H in patients with HER2-amplified early breast cancer. Source: Slamon D et al. SABCS 2009;Abstract 62.

R BCIRG 006: Study Design Eligibility HER2+ by central FISH Accrual: 3,222 (Closed) Eligibility HER2+ by central FISH Node positive or high risk node negative Stratified by nodes and hormone receptor status AC  T R AC  TH TCH AC  T = AC (Adriamycin 60 mg/m2, Cyclophosphamide 600 mg/m2) q 3 weeks x 4 followed by T (Docetaxel 100 mg/m2) q 3 weeks x 4 AC  TH = AC (Adriamycin 60 mg/m2, Cyclophosphamide 600 mg/m2) q 3 weeks x 4 followed by T 100 mg/m2 q 3 weeks x 4. Trastuzumab (H) initiated with T x 1 year TCH = T (75 mg/m2) and Carboplatin (AUC 6) q 3 weeks x 6. H initiated with TC x 1 year Source: Slamon D et al. SABCS 2009;Abstract 62.

BCIRG 006: Tumor Characteristics n = 1073 % AC  TH n = 1074 TCH n = 1075 Number of Nodes (+) 1-3 4-10 > 10 29 38 22 11 24 9 39 23 10 Tumor Size (cm) ≤ 2 > 2 and ≤ 5 > 5 41 53 6 55 7 40 54 ER and/or PR (+) Source: Slamon D et al. SABCS 2009;Abstract 62.

Disease Free Survival (DFS) 3rd Planned Analysis (median follow-up 65 mos) 1 0.9 84% 0.8 81% 75% 0.7 % alive and disease-free 0.6 Patients Events HR (95% C.I.) P 1073 257 1 (reference) 1074 185 0.64 (0.53 - 0.78) <0.001 1075 214 0.75 (0.63 - 0.90) 0.04 AC-T AC-TH 0.5 TCH 0.4 12 24 36 48 60 72 Time (months) Source: With permission Slamon D et al. SABCS 2009;Abstract 62.

Overall Survival 3rd Planned Analysis (median follow-up 65 mos) 1 92% 0.9 91% 87% 0.8 0.7 % alive 0.6 Patients Events HR (95% C.I.) P 1073 141 1 (reference) 1074 94 0.63 (0.48 - 0.81) <0.001 1075 113 0.77 (0.60 - 0.99) 0.038 AC-T AC-TH 0.5 TCH 0.4 12 24 36 48 60 72 Time (months) Source: With permission Slamon D et al. SABCS 2009;Abstract 62.

DFS According to Nodal and Topo IIa Amplification Status Lymph Node Status AC  T AC  TH TCH Lymph node negative (n=309, 310, 309) 85% 93% 90% Lymph node positive (n=764, 764, 766) 71% 80% 78% Lymph nodes ≥ 4 (n=350, 350, 352) 61% 73% 72% Topo IIa Amplification Topo IIa non co-amplified (n=643, 643, 618) 70% 83% Topo IIa co-amplified (n=328, 357, 359) 82% Source: Slamon D et al. SABCS 2009;Abstract 62.

Safety Endpoints No cardiac related deaths were observed in any of the three study arms. Grade 3/4 CHF was lower in the TCH arm. 0.4% with TCH versus 0.7% with AC  T versus 2% with AC  TH. The incidence of >10% decline in LVEF was lower in the TCH arm. 9% with TCH versus 19% with AC  TH versus 11% with AC  T Eight patients in BCIRG 006 have developed acute leukemias to date. Six cases in AC  T, one case in AC  TH and one case in TCH (patient received CHOP for subsequent diagnosis of lymphoma prior to acute leukemia development) Source: Slamon D et al. SABCS 2009;Abstract 62.

BCIRG 006: Therapeutic Index AC  TH n = 1074 TCH n = 1075 DFS Events 185 214 Grade 3 / 4 CHF 21 4 Totals 206 218 Treatment-related leukemias 1 1* Sustained LVEF loss > 10% 194 97 * Leukemia developed after CHOP chemotherapy Source: Slamon D et al. SABCS 2009;Abstract 62.

Conclusions: BCIRG 006 Trastuzumab provides a similar and significant advantage for both DFS and OS in low- and high-risk patients when used either as AC  TH or as TCH. Acute and chronic toxicity profiles of TCH are better than AC  TH. Though there is no statistical advantage, the AC  TH arm had a 29 event numerical advantage in DFS events over that of the TCH arm. Numerical advantage, however, was associated with 5 times more cases of CHF in the AC  TH arm than in the TCH arm. All three regimens showed similar efficacy in a subset of patients with Topo IIa co-amplification. The incremental benefit of AC that is known for HER2+ BC appears restricted to TOPO IIa co-amplified cancers. Source: Slamon D et al. SABCS 2009;Abstract 62.