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Adjuvant systemic therapy in breast cancer

Adjuvant systemic therapy in breast cancer. Targeted therapies Update R. Paridaens Belgian Breast Meeting 04-10-2008. All our therapies Are ( should be ) Targeted …. Efficacy Locate target

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Adjuvant systemic therapy in breast cancer

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  1. Adjuvant systemictherapyin breast cancer Targetedtherapies Update R. Paridaens BelgianBreast Meeting 04-10-2008

  2. All ourtherapies Are (shouldbe) Targeted…. Efficacy Locatetarget Use specificweapon

  3. The oldesttargetedmoleculartherapy ishormonotherapy! Whenreceptors are involved, the principleswillremain the same: Interferewith ligand production Or Block the receptor action

  4. TARGETEGFR (ErbB) Family(HumanEpidermalGrowth Factor Receptors)HER1,2,3,4

  5. Anti – HER2 therapieshavingreached the adjuvant levelfor breast cancer Antibodiestargeting HER2: Trastuzumab TKI : Lapatinib

  6. The FIN HER Trial Randomized trial comparing : 3x Docetaxel 100mg/m2 q3W followed by 3x FEC Versus 9x Vinorelbine 25mg/m2 weeklyfollowed by 3x FEC The 232 pts with HER2 + tumorswererandomized to receive (n=116) or not (n=116) Herceptinweeklyduring the first nineweeks of treatment DFS wassignificantlybetterwithHerceptin: 89% vs 78% (HR O.42, P=0.01) OS wasalsobetter: 96% vs 90% (HR 0.41, P=0.07)

  7. Adjuvant Herceptin FACTS: Efficacy! Cardiotoxicity! Questions: Schedulingwithchemo? Duration? HT? Costs? Are chemoregimens Withoutanthracyclines As efficient and lesstoxic?

  8. TARGETAngiogenesisPathway

  9. Angiogenesis is involved throughout tumour formation, growth and metastasis Premalignant stage Malignant tumour Tumourgrowth Vascularinvasion Dormantmicrometastasis Overtmetastasis (Avascular tumour) (Angiogenicswitch) (Vascularisedtumour) (Tumour cellintravasation) (Seeding indistant organs) (Secondary angiogenesis) Stages at which angiogenesis plays a role in tumour progression Adapted from Poon RT, et al. J ClinOncol 2001;19:1207–25

  10. Genentech 2007: Beyond the Tumor-Targeting Angiogenesis in Cancer

  11. Anti-VEGF antibodies (bevacizumab) Soluble VEGFRs (VEGF-TRAP) VEGF Anti-VEGFR antibodies (IMC-1121b) P P P P P P P P Endothelial cell Small-moleculeVEGFR inhibitors (PTK787, SU11248, ZD6474, BAY 43-9006) Agents Targeting the VEGF Pathway Avastin Sutent Sorafenib Podar and Anderson. Blood. 2005;105:1383

  12. Anti – angiogenictherapieshavingreached the adjuvant levelfor breast cancer Antibodiestargeting VEGF: Bevacizumab (Avastin) ? TKI : Sunitinib (Sutent)? ?Metronomicchemotherapy?

  13. 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.

  14. Anti-VEGF antibody (Bevacizumab) VEGF P P P P P P P P VEGFR-1 VEGFR-2 Endothelial cell Bevacizumab Binds VEGF Presta et al. Cancer Res. 1997;57:4593.

  15. Conclusions Adjuvant setting Targetedtherapy 2008

  16. Targetingtumorsubtypes • ER and/or PR + (Tam? AI?) • HER2 amplification (TTZ? Other? Chemo?) • Triple negative – basal like (Chemo?)

  17. Targeting patient geno/phenotypes • Metaboliccapacity • Familial breast cancer • DNA repairdefects

  18. Tamoxifenless efficient whenmetaboliccapacity (SNP of cytochromes) isaltered?

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