Adjuvant systemic therapy in breast cancer
description
Transcript of Adjuvant systemic therapy in breast cancer
![Page 1: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/1.jpg)
Adjuvant systemic therapyin breast cancer
Targeted therapies Update
R. Paridaens Belgian Breast Meeting
04-10-2008
![Page 2: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/2.jpg)
All our therapies
Are (should be)
Targeted….
Efficacy
Locate target
Use specific weapon
![Page 3: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/3.jpg)
The oldest targeted molecular therapyis hormonotherapy!
When receptors are involved,
the principles will remain the same:
Interfere with ligand production
Or
Block the receptor action
![Page 4: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/4.jpg)
![Page 5: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/5.jpg)
![Page 6: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/6.jpg)
![Page 7: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/7.jpg)
![Page 8: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/8.jpg)
TARGETEGFR (ErbB) Family
(Human Epidermal Growth Factor Receptors)
HER1,2,3,4
![Page 9: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/9.jpg)
![Page 10: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/10.jpg)
![Page 11: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/11.jpg)
Anti – HER2 therapies having reached the adjuvant level for breast cancer
Antibodies targeting HER2: Trastuzumab
TKI : Lapatinib
![Page 12: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/12.jpg)
![Page 13: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/13.jpg)
![Page 14: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/14.jpg)
![Page 15: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/15.jpg)
The FIN HER TrialRandomized trial comparing :3x Docetaxel 100mg/m2 q3W followed by 3x FEC Versus9x Vinorelbine 25mg/m2 weekly followed by 3x FEC
The 232 pts with HER2 + tumors were randomized to receive (n=116) or not (n=116) Herceptin weekly during the first nine weeks of treatment
DFS was significantly better with Herceptin: 89% vs 78% (HR O.42, P=0.01) OS was also better: 96% vs 90% (HR 0.41, P=0.07)
![Page 16: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/16.jpg)
Adjuvant Herceptin
FACTS:
Efficacy!Cardiotoxicity!
Questions:
Scheduling with chemo?Duration?HT?Costs?
Are chemo regimensWithout anthracyclinesAs efficient and less toxic?
![Page 17: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/17.jpg)
![Page 18: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/18.jpg)
TARGET
Angiogenesis Pathway
![Page 19: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/19.jpg)
Angiogenesis is involved throughout tumour formation, growth and
metastasis
Stages at which angiogenesis plays a role in tumour progression
Premalignantstage
Malignanttumour
Tumourgrowth
Vascularinvasion
Dormantmicrometastasis
Overtmetastasis
(Avasculartumour)
(Angiogenicswitch)
(Vascularisedtumour)
(Tumour cellintravasation)
(Seeding indistant organs)
(Secondaryangiogenesis)
Adapted from Poon RT, et al. J Clin Oncol 2001;19:1207–25
![Page 20: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/20.jpg)
Genentech 2007: Beyond the Tumor-Targeting Angiogenesis in Cancer
![Page 21: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/21.jpg)
Agents Targeting the VEGF Pathway
Podar and Anderson. Blood. 2005;105:1383
PPP
PPPP
P
Endothelial cell
Small-moleculeVEGFR inhibitors
(PTK787, SU11248, ZD6474, BAY 43-9006)
Anti-VEGFR antibodies(IMC-1121b)
VEGF
Anti-VEGF antibodies(bevacizumab)
Soluble VEGFRs(VEGF-TRAP)Avasti
n
SutentSorafenib
![Page 22: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/22.jpg)
Anti – angiogenic therapies having reached the adjuvant level for breast cancer
Antibodies targeting VEGF: Bevacizumab (Avastin)
? TKI : Sunitinib (Sutent)?
?Metronomic chemotherapy?
![Page 23: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/23.jpg)
Bevacizumab
• Recombinant humanized monoclonal IgG1 antibody
• Recognizes all isoforms of VEGF1
• Estimated half-life approximately 20 days (range, 11-50 days)
Presta et al. Cancer Res. 1997;57:4593.
![Page 24: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/24.jpg)
Bevacizumab Binds VEGF
VEGFR-2VEGFR-1PPP
PPPP
P
Endothelial cell
VEGF
Anti-VEGF antibody
(Bevacizumab)
Presta et al. Cancer Res. 1997;57:4593.
![Page 25: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/25.jpg)
![Page 26: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/26.jpg)
![Page 27: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/27.jpg)
![Page 28: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/28.jpg)
![Page 29: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/29.jpg)
Conclusions
Adjuvant setting
Targeted therapy 2008
![Page 30: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/30.jpg)
Targeting tumor subtypes
• ER and/or PR + (Tam? AI?)
• HER2 amplification (TTZ? Other? Chemo?)
• Triple negative – basal like (Chemo?)
![Page 31: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/31.jpg)
Targeting patient geno/phenotypes
• Metabolic capacity
• Familial breast cancer
• DNA repair defects
![Page 32: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/32.jpg)
Tamoxifen less efficient when metabolic capacity (SNP of cytochromes) is altered?
![Page 33: Adjuvant systemic therapy in breast cancer](https://reader033.fdocuments.in/reader033/viewer/2022051402/568158b9550346895dc60359/html5/thumbnails/33.jpg)