1 / 60

Terapia Neoadiuvante nella malattia HER-2 positiva: Trasferibilità nella pratica clinica

Terapia Neoadiuvante nella malattia HER-2 positiva: Trasferibilità nella pratica clinica. Vincenzo Adamo. UOC Terapie Integrate in Oncologia AOU Policlinico ”G.Martino” Messina. Sequence of Treatment for Primary Breast Cancer. Diagnosis and Staging Surgical Resection

claire
Télécharger la présentation

Terapia Neoadiuvante nella malattia HER-2 positiva: Trasferibilità nella pratica clinica

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Terapia Neoadiuvante nella malattia HER-2 positiva: Trasferibilità nella pratica clinica Vincenzo Adamo UOC Terapie Integrate in Oncologia AOU Policlinico ”G.Martino” Messina

  2. Sequence of Treatment for Primary Breast Cancer Diagnosis and Staging Surgical Resection Adjuvant systemic treatment Diagnosis and Staging Neoadjuvant systemic therapy Surgical Resection Adjuvant therapy

  3. The Rational for Neoadjuvant Therapy in Breast Cancer: Which Patients? • Traditionally: Neoadjuvant systemic therapy should be considered for patients inoperable at onset: T4, clinical N2-N3 • New data: supporting preoperative or neoadjuvant systemic therapy in primary operable breast cancer patients • NCCN Guidelines 2011:neoadjuvant chemotherapy or trastuzumab plus chemotherapy should be considered for HER2+ patients

  4. Goals of Neoadjuvant Theapy in Breast Cancer • Make tumours more operable, increase the rate of breast conserving surgeries • Improve prognosis of certain disease subtypes (i.e. HER2+) • Have a better idea of prognosis based on response to neoadjuvant treatment • Allow patients to start treatment earlier • Reduce the extent of surgery required in breast and axylla • Improve DFS and OS using pathological response rate for selection of subsequent treatment in individual patients

  5. Parametres to assessed in clinical practice • pCR and Treatment Outcomes • Status lymph node (sentinel node biopsy) • Instrumental evaluation with MRI and PET • Toxicity

  6. Definition of pCR • Different definition of pCR are in use: - Absence of invasive cancer in the breast - Absence of invasive cancer in the breast and in the axillary lymph nodes. - Absence of invasive and in situ cancer cells in the breast and in the axillary nodes • There is high degree of concordance between the different definition • With very definition pCR identifies cases with favorable disease Marchiò C. & Sapino A. JNCI Monogr 2011;43:86–90

  7. Tumor size & Tumor grade Histological type ER/PgR Her2/neu Proliferative markers ( Ki-67/MIB-1, PCNA) Treatment & MDR-1/pgp Putative Predictive Factors of pCR

  8. pCR to Neoadjuvant Chemotherapy is correlated with improved DFS & OS (NSABP B-27) Disease free-survival Overall Survival There was no significant difference in overall survival (OS) between the treatment arms (data not shown). Pathologic CR (pCR) was a significant predictor of OS, regardless of treatment. Bear HD, et al. J ClinOncol. 2006;24(13):2019-2027.

  9. Outcomes of Neoadjuvant Trials with unselected tumor characteristics Mazouni C, et al. J Clin Oncol. 2007

  10. Intrinsic sub-types have different prognosis and different response to NACT

  11. MD Anderson Neoadjuvant TrialDFS at 72 months FU Budzar A. et al Asco 2009

  12. “ ..if indicated, the majority of the Panel considered that the neoadjuvant chemotherapy regimen should include both a taxane and an anthracycline and(for HER2-positive disease) an anti-HER2 drug. Thus, the choice of a regimen for adjuvant or neoadjuvant chemotherapy might be made using similar criteria..’’ Goldhirsch A, et al. Ann Oncol. 2009;20(8):1319-1329.

  13. Impact of treatment characteristics on the pCR Untch M. et al J Nat Cancer Inst Monogr 2011.

  14. Impact of treatment characteristics on the pCR Untch M. et al J Nat Cancer Inst Monogr 2011.

  15. Schedules and pCR rate in HER2-positive disease V, vinorelbine; X, capecitabine; C, carboplatin ;FEC, 5-fluorouracil, epirubicin, cyclophosphamide.

  16. Pre and Post-operative Chemotherapy plus Trastuzumab Improve DSF

  17. … Future Clinical Practice….

  18. Anti-HER2 Treatment:Mechanisms of action

  19. Three Neoadjuvant Trials Using Targeted Therapies for HER-2 Positive BC

  20. pCRS in Three Trials with Target Therapies

  21. Guarneri V. et al. ASCO 2011

  22. Efficacy: Breast and Axillary pCR Rate • Guarneri V. et al. ASCO 2011

  23. Status lymph node (sentinel node biopsy)

  24. SLNB in relation to neoadjuvant therapy • Which is the aim of SLNB in breast cancer patients? • Which patients are usually receiving neoadjuvant? • Is there a role of SLNB in patients undergoing neoadjuvant therapy? • Should SLNB be performed before or after neoadjuvant therapy? • Are there sufficient data supporting either approach ? St Gallen 2007, Annals of Oncol 18: 1133–1144, 2007

  25. SLN Biopsy Prior to Therapy Disadvantages • Two operations • Potentially delays start of chemotherapy Advantages • Higher identification rate • Lower false negative rate St Gallen 2007, Annals of Oncol 18: 1133–1144, 2007

  26. The Role of SNLB Inflammatory breast cancer not indicated • breast lymphedema, due to occluded lymphatics by metastatic cells inadequate lymphatic drainage mapping agents would also be trapped and not travel to the SLN false-negative rate very high Locally Advanced (large tumor size) - Palpable lymphadenopathy  FNA –No Role for SNLB - Non palpable or Clinically negative LNsSLNB is acceptable - Before or after neo-adjuvant chemotherapy ? St Gallen 2007, Annals of Oncol 18: 1133–1144, 2007

  27. Marchiò C. & Sapino A. JNCI Monogr 2011;43:86–90

  28. St Gallen 2011:SN and ALND

  29. Downstaging Axilla & Complete Axillary Response • Strong prognostic factor Axillary pCR: 93% Residual disease: 60% Hennessey BT, et al. J Clin Oncol.2005;23(36):9304-9311.

  30. Instrumental evaluation: MRI and PET and Neoadjuvant Chemo in HER2BC

  31. MRI: Evaluation Neoadjuvant Chemotherapy • MRI highest accurracy for monitoring chemotherapy • Change in (residual) tumor size, signal intensity, and contrast kinetics • Underestimation possible! Mc Guire K.P. et al.Ann Surg Oncol 2011

  32. MRI Staging after NACT : Does Tumor Biology Affect Accuracy? MRI response versus pathologic response by tumor subtype. Discrimination and predictive value (a) overall, (b) luminal A/B, and (c) HER2+/TN Mc Guire K.P. et al.Ann Surg Oncol 2011

  33. Early metabolic responseusing PET in Neoadjuvant BC Keam B.et al.BMC Cancer 2011

  34. Toxicity and neoadjuvant Chemotherapy in HER2BC

  35. 12 months 12 months End of trastuzumab End of trastuzumab LVEF during and after therapy HER2-positive trastuzumab HER2-positive control 80 80 60 60 LVEF 40 40 20 20 Baseline Baseline 18 months 24 months 18 months 24 months End of CMF End of CMF Gianni L. et al Lancet 2010

  36. 30 30 20 20 10 10 0 0 -10 -10 -20 -20 -30 -30 12 months 12 months End of trastuzumab End of trastuzumab LVEF change during and after therapy HER2-positive trastuzumab HER2-positive control LVEF change (% units) 18 months 24 months 24 months 18 months End of CMF End of CMF Gianni L. et al Lancet 2010

  37. Cardiac Toxicity & Trastuzumab Gianni L. et al Lancet 2010

  38. Cardiac monitoring guidance: Trastuzumab • All patients for Herceptin treatment should undergo baseline cardiac assessment prior to treatment initiation • For patients with EBC, cardiac assessment should be performed every 3 months during treatment and at 6, 12 and 24 months following cessation of treatment • For patients with MBC, cardiac function should be monitored during treatment (eg every 3 months) • Patients who develop asymptomatic cardiac dysfunction may benefit from more frequent monitoring (eg every 6-8 weeks) CGCC, Cardiac Guidelines Consensus Committee;EMEA, European Medicines Evaluation Agency

  39. HER2 BC & Neoadjuvant St Gallen 2011

  40. Intrinsic sub-types have different prognosis and different response to NACT

  41. Comments and questions Conclusive comments • NACT should be considered as an option for every woman as far as the indication for adjuvant treatment has been confirmed • Many good quality clinical trials suggest that trastuzumab should be incorporated in the preoperative treatment of women with HER2-pos (..NCCN guidelines). open questions • the preferred combination chemotherapy with trastuzumab • the optimal duration of trastuzumab in pts who achieve a pCR after preoperative chemotherapy.

  42. The end • Stop here

  43. NOAH Neoadjuvant Trial:pCR Rates Gianni L. et al. Lancet 2010

  44. pCR After NACT Plus Trastuzumab Predicts Favorable Survival in HER2+ BC: Results From the TECHNO Untch M. et al, JCO 2011

  45. Neoadjuvant Therapy (NAT):Potential Advantages • Improved Tumor Downstaging • Inoperable Operable • Mastectomy BCS • Provides in vivo assessment of anti-tumor effects • Provides opportunity to assess surrogate biological endpoints • Early initiation of systemic therapy • Inhibition of post-surgical growth spurt • May expedite new drug development no

  46. pCR and Treatment Outcome • pCR is a robust measure of therapeutic effects and surrogate a DFS in responder • Increase pCR rate should correspond to improved efficacy in the overall patient population • Prediction of pCR should predict for benefit and allow for tailoring treatment to indivudual tumor characteristics no

  47. BC after NACT:The M.D. Anderson Cancer Center Experience no Chen AM et al. J Clin Oncol. 2004;22:2303-2312.

More Related