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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.

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Terapia Neoadiuvante Revisione delle evidenze scientifiche

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  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”

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