Metastatic Breast Cancer in 2015 Are we making progress? Vernon - - PowerPoint PPT Presentation

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Metastatic Breast Cancer in 2015 Are we making progress? Vernon - - PowerPoint PPT Presentation

Jan 10, 2024 490 likes •912 views

Metastatic Breast Cancer in 2015 Are we making progress? Vernon Harvey Auckland - November 2015 Systemic Management of Metastatic Breast Cancer Remains incurable Aims of therapy - Quality of life - Prolongation of life - Identify

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Metastatic Breast Cancer in 2015

Are we making progress?

Vernon Harvey Auckland - November 2015

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Systemic Management of Metastatic Breast Cancer

Remains incurable Aims of therapy

  • Quality of life
  • Prolongation of life
  • Identify ‘best’ therapy

How do we achieve this?

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Systemic Management of Metastatic Breast Cancer

Options

Hormone Therapy Chemotherapy Biological Therapy Symptom Control

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Metastatic Breast Cancer

General Principles Hormone therapy Chemotherapy *

(with Herceptin if HER2+)

Symptom Control * Some prefer chemotherapy first for life threatening disease

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Endocrine options in MBC

  • Premenopausal

 Ovarian Ablation  Tamoxifen  ?Ovarian Ablation and AI

  • Postmenopausal

 Aromatase Inhibitors  Tamoxifen  Progestogens  Faslodex

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60% response (if ER+) Average duration 9 to 12 months May respond to subsequent hormones

Results of Hormone Treatment

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Systemic Management of Breast Cancer

Chemotherapy

CMF Adriamycin Taxanes Vinorelbine Capecitabine Combination chemotherapy Herceptin

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50 - 60 % response Average duration 9 to 12 months Responses tend to get shorter

Results of Chemotherapy

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Limitations of Chemotherapy

  • No drug clearly superior
  • Combinations not superior to sequential use

(and more toxic)

  • Higher doses not better
  • Lower doses not “kinder”
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Metastatic Breast Cancer

Endocrine Therapy

(ER and/or PR + only)

Single drug Sequential therapy Continue to progression Control in 30-60% Average duration 9- 12 mths Wide variation Chemotherapy

(ER/PR- or failed hormones)

Single or combination Sequential therapy Duration limited by toxicity Control in 30-60% Average duration 9-12 mths Wide variation Achievements

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Has anything changed?

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Changing Perspectives

Why?

Numerous new medications but limited improvements in survival Enormous effort for limited benefit to date

What has changed?

Improved understanding of cancer biology Greater recognition of therapeutic targets Need to speed up drug development

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Biology is Key

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The Herceptin Story

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erb-b1 EGFR HER1 neu Erb-b2 HER2 Erb-b3 HER3 Erb-b4 HER4 HRG (NRG1) Tyrosine kinase domain Ligand binding domain Transmembrane

Mendelsohn and Baselga. Oncogene. 2000;19:6550. Olayioye et al. EMBO J. 2000;19:3159. Prigent and Lemoine. Prog Growth Factor Res. 1992;4:1. Harari and Yarden. Oncogene. 2000;19:6102. Earp et al. Breast Cancer Res Treat. 1995;35:115.

The EGFR/HER Family

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Slamon D et al. N Engl J Med 2001;344:783-792

Progression-free Survival in patients on Chemotherapy plus Trastuzumab or Chemotherapy Alone (Panel A) and Whether Anthracycline and Cyclophosphamide (Panel B)

  • r Paclitaxel (Panel C)
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The fascinating history of Herceptin

Phase I IND for rhuMAb HER2 Murine HER2 / neu gene cloned Human HER2 gene cloned muMAb 4D5 Association of HER2 with poor clinical outcome Paclitaxel + H and H mono US approval Paclitaxel + H and H mono EU approval 1st IA of HERA

1992 1985 1990 1981 1987 2000 1998 2005 2006

HERA recruitment

  • pens

HERA 2-year follow-up Adjuvant H approval

2008

HERA 4-year follow-up and 1-year H vs 2-year H IA

2011

HERA final analysis 1-year H vs 2-year H

HER2, human epidermal growth factor receptor 2; H, Herceptin; IA, interim analysis

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Barbara Bradfield

The first patient with MBC treated with Herceptin – 10 years disease free

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Lapatinib

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Pertuzumab and trastuzumab: potential for additive efficacy

Pertuz uzumab umab

HER3 R3 HER2 R2

Trastuz uzuma umab

  • Pertuzuma

zumab b and trastuz tuzumab umab bind d to differe rent t epitopes es

  • n HER2
  • May have compleme

ementa tary ry mechanism sms of action

  • This may result

lt in additi tive ve efficacy cy when used together er AKT PDK1

cell cycle control ↓ apoptosis survival

Cyclin D1 p27 BAD GSK3 NFB mTOR

P P P P P

proliferation angiogenesis P13K

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Trastuzumab-Emtansine (T-DM1)

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Reversing Endocrine Resistance

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Reversing Endocrine Resistance

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Paloma 01 trial

Palbociclib + letrozole vs Letrozole

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Involving the Immune System

Disease shrinkage in 20%

  • f triple negative

breast cancer Keynote 012 trial SABCS 2024

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We are moving forward……………

but never as quickly as we want or patients need

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Systemic Management of Breast Cancer

Additional Measures Radiation therapy Orthopaedic procedures Bisphosphonates Pleurocentesis Abdominocentesis etc

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And all the while………LIVE

Thank you very much