William J. Gradishar MD, FACP Betsy Bramsen Professor of Breast Oncology Director, Maggie Daley Center For Women's Cancer Care Robert H. Lurie Comprehensive.

Slides:

Advertisements

Similar presentations

William J. Gradishar MD, FACP Betsy Bramsen Professor of Breast Oncology Director, Maggie Daley Center For Women's Cancer Care Robert H. Lurie Comprehensive.

Advertisements

Extending life for women with HER2-positive MBC

Metastatic HER2-Positive Breast Cancer: Treatment Selection and Sequencing in the First Line and Beyond Moderator: Joseph Gligorov, MD, PhD Head, Cancer.

Open Clinical Trials: What’s Out There Now Paula D. Ryan, MD, PhD

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

Fabio Puglisi Dipartimento di Oncologia Azienda Ospedaliero Universitaria di Udine Antiangiogenic Treatment Mediterranean School of Oncology.

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

Assistant Professor of Medicine Dana-Farber Cancer Institute

Phase III Study Comparing Gemcitabine plus Cetuximab versus Gemcitabine in Patients with Locally Advanced or Metastatic Pancreatic Adenocarcinoma Southwest.

CS-1 Results of the Phase 3 Clinical Trials of Abraxane vs. Taxol in Metastatic Breast Cancer William J. Gradishar, MD, FACP Professor of Medicine Northwestern.

First-Line TKI Use in EGFR Mutation-Positive NSCLC

A Phase III, Randomized, Double-Blind, Placebo-Controlled Registration Trial to Evaluate the Efficacy and Safety of Placebo + Trastuzumab + Docetaxel vs.

Bevacizumab: Antiangiogenic therapy for breast cancer: where do we stand? Fortunato Ciardiello Division of Medical Oncology, Department of Clinical and.

Taxane-pretreated metastatic breast cancer (MBC): investigational agents TTP = median time to disease progression OS = median overall survival.

Cabozantinib (XL184) in Metastatic Castration-Resistant Prostate Cancer (mCRPC): Results from a Phase II Randomized Discontinuation Trial Hussain M et.

Use of Chemotherapeutic and Biologic Agents in Metastatic Breast Cancer Breast Cancer Update Medical Oncology Educational Forum May 21, 2005 Kathy D Miller.

Assistant Professor of Medicine Dana-Farber Cancer Institute

Phase III Trial of Pazopanib in Locally Advanced and/or Metastatic Renal Cell Carcinoma Sternberg CN et al. ASCO 2009; Abstract (Oral Presentation)

Cetuximab + Cisplatin in Estrogen Receptor-Negative, Progesterone Receptor-Negative, HER2-Negative (Triple-Negative) Metastatic Breast Cancer: Results.

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

Randomized Phase III Trial Comparing FOLFIRINOX (F: 5FU/Leucovorin [LV], Irinotecan [I], and Oxaliplatin [O]) versus Gemcitabine (G) as First-Line Treatment.

BASED ON PROTOCOL VERSION 1 SEPTEMBER 2012 A new study evaluating an investigational drug to treat patients with HER2-positive metastatic gastroesophageal.

Activity and Tolerability of Afatinib (BIBW 2992) and Cetuximab in NSCLC Patients with Acquired Resistance to Erlotinib or Gefitinib Janjigian YY et al.

Copyright © 2010, Research To Practice, All rights reserved. Current Clinical and Future Developmental Paradigms Involving Molecular Pathways in Breast.

E2100 A Randomized Phase III Trial of Paclitaxel versus Paclitaxel plus Bevacizumab as First- Line Therapy for Locally Recurrent or Metastatic Breast Cancer.

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.

These slides are intended to educate the scientific and medical community and keep them fully informed about continuing progress, as is their right, stipulated.

A Comparison of Fulvestrant 500 mg with Anastrozole as First-line Treatment for Advanced Breast Cancer: Follow-up Analysis from the FIRST Study Robertson.

Final Efficacy Results from OAM4558g, a Randomized Phase II Study Evaluating MetMAb or Placebo in Combination with Erlotinib in Advanced NSCLC Spigel DR.

AVADO TRIAL David Miles Mount Vernon Cancer Centre, Middlesex, United Kingdom A randomized, double-blind study of bevacizumab in combination with docetaxel.

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

Results of a Randomized Phase 2 Study of PD , a Cyclin ‐ Dependent Kinase (CDK) 4/6 Inhibitor, in Combination with Letrozole vs Letrozole Alone.

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

Gemcitabine With or Without Cisplatin in Patients with Advanced or Metastatic Biliary Tract Cancer (ABC): Results of a Multicentre, Randomized Phase III.

Impact of Bevacizumab (Bev) on Efficacy of Second-Line Chemotherapy (CT) for Triple- Negative Breast Cancer: Analysis of RIBBON-2 Brufsky A et al. Proc.

Agency Review of sNDA SE-006 DOXIL for Ovarian Cancer Division of Oncology Drug Products Office of Drug Evaluation 1 Center for Drug Evaluation.

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.

Responses to Subsequent Anti-HER2 Therapy After Treatment with Trastuzumab-DM1 in Women with HER2- Positive Metastatic Breast Cancer 1 A Phase Ib/II Trial.

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

North Central Cancer Treatment Group Randomized Phase II Trial of Panitumumab, Erlotinib, and Gemcitabine (PGE) versus Erlotinib-Gemcitabine (GE) in Patients.

PHASE II RANDOMIZED STUDY OF TRASTUZUMAB EMTANSINE VERSUS TRASTUZUMAB PLUS DOCETAXEL IN PATIENTS WITH HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 – POSITIVE.

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.

CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016 Phase II MONARCH 1: CDK4/6 Inhibitor Abemaciclib in HR+/HER2- MBC.

CCO Independent Conference Coverage

CCO Independent Conference Coverage

PALOMA-2: Addition of Palbociclib to Frontline Letrozole Significantly Improves PFS in Postmenopausal ER+/HER2- Advanced Breast Cancer CCO Independent.

CCO Independent Conference Highlights

Alessandra Gennari, MD PhD

Chicago 2008: Post - ASCO Analysis: Metastatic Breast Cancer

A Single-Arm Phase IIIb Study of Pertuzumab and Trastuzumab with a Taxane as First-Line Therapy for Patients with HER2-Positive Advanced Breast Cancer.

CCO Independent Conference Highlights

Gajria D et al. Proc SABCS 2010;Abstract P

Maintenance Lapatinib After Chemotherapy in HER1/2-Positive Metastatic Bladder Cancer CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting*

Blackwell KL et al. SABCS 2009;Abstract 61

Vahdat L et al. Proc SABCS 2012;Abstract P

What do we do after FOLFIRINOX? Gemcitabine-Based Therapy is Standard

CCO Independent Conference Highlights

Swain SM et al. Proc SABCS 2012;Abstract P

Her2-positive breast cancer: updating current best practice

Barrios C et al. SABCS 2009;Abstract 46.

Krop I et al. SABCS 2009;Abstract 5090.

A Report from ECCO 14 Oral Chemotherapy in Breast Cancer

Untch M et al. Proc SABCS 2010;Abstract P

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

Program Goals. Single vs Dual HER2 Blockade for Metastatic HER2-Positive Breast Cancer.

Baselga J et al. SABCS 2009;Abstract 45.

Optimizing Targeted Therapy for HER2-Positive Advanced Breast Cancer: Considerations for Previously Treated Disease.

Efficacy of BSI-201, a PARP Inhibitor, in Combination with Gemcitabine/Carboplatin (GC) in Triple Negative Metastatic Breast Cancer (mTNBC): Results.

Maximizing Disease-Free Survival in Early-Stage HER2-Positive Breast Cancer.

Presentation transcript:

William J. Gradishar MD, FACP Betsy Bramsen Professor of Breast Oncology Director, Maggie Daley Center For Women's Cancer Care Robert H. Lurie Comprehensive Cancer Center Northwestern University Feinberg School of Medicine Chicago, IL Future therapeutics for HER2 positive metastatic breast cancer

‘Irreversible’ tyrosine kinase inhibitors  Irreversible TKIs form covalent bonds with tyrosine kinase Irreversible bond  TK remains inhibited until new receptor/TK complex can be synthesized  Afatinib and neratinib are HER1[EGFR]/HER2 TKIs in development Awada et al, Cancer Treat Rev. 2012;38:

Afatinib in trastuzumab refractory MBC  Patients with pretreated MBC (n=41) Median prior lines of chemotherapy: 3 >1 year trastuzumab therapy: 68% Response to trastuzumab: ► CR: 2 ► PR: 13 ► SD: 13  Response to afatinib: PR: 4 (10%) SD: 15 (37%) (6 patients were not evaluable) Median PFS: 15 weeks Median OS: 61 weeks.  Adverse events: Grade 3 or 4 diarrhea Rash Lin et al, Breast Cancer Res Treat. 2012;133:

Ongoing LUX-breast clinical trials with afatinib in breast cancer 1. Harbeck et al, J Clin Oncol. 2012;30 (suppl); abstr TPS Hickish et al, J Clin Oncol. 2012;30 (suppl); abstr TPS Joensuu & Kaci, J Clin Oncol. 2012;30 (suppl); abstr TPS647. LUX-breast 1 1 LUX-breast 2 2 LUX-breast 3 3 Study design Randomized Phase IIIOpen-label Phase IIRandomized Phase II Patients Target 780 HER2 + MBC Progression on or after 1 prior trastuzumab regimen Target 120 HER2 + MBC Progression after adjuvant / neoadjuvant trastuzumab and / or lapatinib Target 120 HER2 + MBC Progressive / recurrent brain metastases during / after prior trastuzumab or lapatinib Treatment arms Afatinib (40 mg) + vinorelbine vs Trastuzumab + vinorelbine Afatinib 40 mg followed by afatinib + paclitaxel or Vinorelbine after progression Afatinib (40 mg) vs Afatinib (40 mg) + vinorelbine vs Investigator’s choice Primary endpoint PFSObjective response ratePatient benefit (progression or absence of CNS disease)

Neratinib in patients with advanced HER2 positive breast cancer  Open label study in patients with stage IIIB/C and IV breast cancer  n=136 patients Prior trastuzumab (n=66; 63 evaluable) No prior trastuzumab (n=70; 64 evaluable)  Main adverse events; Diarrhea (including grade 3/4 in 29 patients), nausea, vomiting, and fatigue Burstein et al, J Clin Oncol. 2010;28: Prior T (n=63) No prior T (n=64) 16 week PFS (%)5978 Median PFS (weeks) Objective response rate (%) 2456 Clinical benefit (PR, SD) rate (%) 3369

Summary  The options available for metastatic/ advanced HER2 positive breast cancer have changed with the availability of pertuzumab and, likely in 2013 trastuzumab emtansine  In addition to antibody based technology, another promising approach are the ‘irreversible’ tyrosine kinase inhibitors These form covalent, irreversible bonds and thus demonstrate a prolonged inhibition of the HER2 TK  Clinical trials are ongoing to confirm the initial Phase IIa results