1 / 27

Terapia Neoadiuvante Revisione delle evidenze scientifiche

Terapia Neoadiuvante Revisione delle evidenze scientifiche. Valentina Guarneri Nonantola, 19 Novembre 2011. Preoperative vs postoperative, Overall Survival. DDFS o OS???. The Cochrane Library, Issue 3, 2008. pCR vs residual disease, Overall Survival. The Cochrane Library, Issue 3, 2008.

thi
Download Presentation

Terapia Neoadiuvante Revisione delle evidenze scientifiche

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 NeoadiuvanteRevisione delle evidenze scientifiche Valentina Guarneri Nonantola, 19 Novembre 2011

  2. Preoperative vs postoperative, Overall Survival DDFS o OS??? The Cochrane Library, Issue 3, 2008

  3. pCR vs residual disease, Overall Survival The Cochrane Library, Issue 3, 2008

  4. NEOADJUVANT P-FEC TRASTUZUMAB IN HER2+ OPERABLE BREAST CANCER Buzdar, J Clin Oncol 2005 Buzdar AU, Clin Cancer Res 2007

  5. NOAH HER2-negative LABC(IHC 0/1+) (n=99) ATq3w x 3 cycles Tq3w x 4 cycles CMFq4w x 3 cycles Surgery followed byradiotherapya HER2-positive LABC(IHC 3+ or FISH+) (n=115) (n=113) H + ATq3w x 3 cycles ATq3w x 3 cycles H + T q3w x 4 cycles Tq3w x 4 cycles H q3w x 4 cycles+ CMF q4w x 3 cycles CMFq4w x 3 cycles Surgery followed byradiotherapya Surgery followed byradiotherapya 19 crossed over to H H continued q3wto week 52

  6. Gianni L, Lancet 2010

  7. HR negative, or HR+ with cN+

  8. GEPAR-QUATTRO: EFFICACY OUTCOMES 80 70 60 50 40 30 20 10 0 ypT0 ypTis ypT0/is, N0 ypN0 Untch M, J Clin Oncol 2010

  9. Untch M et al, J Clin Oncol 2011

  10. NEO-ALTTO STUDY DESIGN Invasive operable HER2+ BC T > 2 cm (inflammatory BC excluded) LVEF  50% N=450 lapatinib lapatinib paclitaxel R A N D O M I Z E S U R GE R Y FEC X 3 trastuzumab trastuzumab paclitaxel • Stratification: • T ≤ 5 cm vs. T > 5 cm • ER or PgR + vs. • ER & PgR – • N 0-1 vs. N ≥ 2 • Conservative surgery • or not lapatinib lapatinib trastuzumab trastuzumab paclitaxel + 12 wks 6 wks 34 weeks 52 weeks of anti-HER2 therapy Baselga J et al. SABCS 2010

  11. Neo-ALLTO: PATHOLOGIC RESPONSE L: lapatinib; T: trastuzumab; L+T: lapatinib plus trastuzumab pCR pathologic complete response Baselga J et al. SABCS 2010

  12. CHER LOB Trial: study plan TXL 80 mg/m2   RANDOMI ZATI ON A CORE BI OPSY S URGE RY Chemotherapy   B  Lapatinib 1500 mg/daily   C Lapatinib 1000 mg/daily 5 FU 600 mg/m2 Epi 75 mg/m2 CTX 600 mg/m2 Trastuzumab 2 mg/kg Guarneri V, ASCO 2011

  13. CHER-LOB: EFFICACY OUTCOMES 90 80 70 60 50 40 30 20 10 0 Arm A:CT + trastuzumab Arm B: CT + lapatinib Arm C: CT + trastuzumab/lapatinib Breast conservation Node negativity pCR (breast & axilla) Guarneri V, ASCO 2011

  14. NEOSPHERE: STUDY DESIGN FEC q3w x 3 trastuzumab q3w cycles 5–17 FEC q3w x 3 trastuzumab q3w cycles 5–17 docetaxel q3w x 4→FEC q3w x 3 trastuzumab q3w cycles 5–17 FEC q3w x 3 trastuzumab q3w cycles 5–21 TH (n=107)docetaxel + trastuzumab S U R G E R Y Patients with operable or locally advanced /inflammatory* HER2-positive BC Chemo-naïve & primary tumors >2cm (N=417) THP (n=107)docetaxel + trastuzumab +pertuzumab HP (n=107)trastuzumab + pertuzumab TP (n=96)docetaxel + pertuzumab Study dosing: q3w x 4 BC, breast cancer; FEC, 5-fluorouracil, epirubicin and cyclophosphamide*Locally advanced=T2–3, N2–3, M0 or T4a–c, any N, M0; operable=T2–3, N0–1, M0; inflammatory = T4d, any N, M0H, trastuzumab; P, pertuzumab; T, docetaxel Gianni L et al. SABCS 2010

  15. NEOSPHERE: pCR RATES p = 0.0198 p = 0.0141 p = 0.003 50 40 pCR, %  95% CI 45.8 30 20 29.0 24.0 10 16.8 0 H, trastuzumab; P, pertuzumab; T, docetaxel TH THP HP TP 6 Gianni L et al. SABCS 2010

  16. HORMONE RECEPTOR STATUS AND pCR

  17. pCR BY HORMONE RECEPTOR STATUS L: lapatinib; T: trastuzumab; L+T: lapatinib plus trastuzumab pCR pathologic complete response HR: hormone receptors Baselga J et al. SABCS 2010

  18. CHER-LOB: pCR rate by HR 60 56.2% 50 40 35.7% 35.7% 30 26.6% 25% 22.7% 20 10 HR+ HR- HR+ HR- HR+ HR- 0 Arm A (CT + T) Arm B (CT +L) Arm C (CT + T + L) T: trastuzumab; L: lapatinib; T+L: trastuzumab plus lapatinib

  19. NEOSPHERE: pCR AND HORMONE RECEPTORS STATUS ER or PR pos ER and PR neg 70 60 50 63.2 40 pCR, %  95% CI 30 20 36.8 30.0 29.1 10 26.0 20.0 17.4 5.9 0 H, trastuzumab; P, pertuzumab; T, docetaxel TH THP HP TP Gianni L et al. SABCS 2010

  20. Chang, ASCO 2011

  21. Chang, ASCO 2011

  22. PST IN HER2+ OPERABLE BREAST CANCER: KEY FINDINGS • Patient selection is mandatory for the integration of novel agents in cancer treatment • Chemotherapy + trastuzumab is the gold standard • Double-HER2 blockade increases the pCR rate • Endocrine pathway is still important even in presence of HER2 co-expression • A dual anti-HER2 blockade + endocrine therapy is promising • The preoperative setting is ideal to test new combinations through the “window of opportunity model”

More Related