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Neoadjuvant trials: Study designs

Epirubicin + cyclophosphamide + trastuzumab or lapatinib. Trastuzumab (1 year total therapy). Docetaxel + trastuzumab or lapatinib. GeparQuinto (P hase III). Neoadjuvant trials: Study designs. Neoadjuvant therapy. Adjuvant therapy. S U R G E R Y. FEC (3 cycles).

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Neoadjuvant trials: Study designs

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  1. Epirubicin +cyclophosphamide + trastuzumab or lapatinib Trastuzumab(1 year total therapy) Docetaxel + trastuzumab or lapatinib GeparQuinto (Phase III) Neoadjuvant trials: Study designs Neoadjuvant therapy Adjuvant therapy S U R G E R Y FEC (3 cycles) Trastuzumab (to complete 1 year) Trastuzumaband/orpertuzumab+/- docetaxel NeoSphere(Phase II) Trastuzumab + FEC (3 cycles) (to complete 1 year) Docetaxel* (4 cycles) Laptinib and / or trast-uzumab Paclitaxel+ lapatinib and/or trastuzumab Lapatinib and / or trastuzumab (34 weeks) FEC (3 cycles) NeoALTTO(Phase III) 0 -24 12 21 52 70 -18 -12 Weeks FEC, 5-fluorouracil + epirubicin + cyclophosphamide*Docetaxel only given to patients receiving chemotherapy-free neoadjuvant therapy • www.clinicaltrials.gov

  2. Neoadjuvant treatment regimens • www.clinicaltrials.gov

  3. S U R G E R Y S U R G E R Y L 6 weeks  L + PAC12 weeks FEC q3w x 3 → L 34 weeks E + C +H q3w x 4 T + H q3w x 4 H q3w 6 months H 6 weeks  H + PAC12 weeks FEC q3w x 3 → H 34 weeks NeoALTTO study design2 n=455 GeparQuinto study design1 n=615 E + C q3w x 4+ L 1250 mg qd T q3w x 4+ L 1250 mg qd H q3w 1 year L + H 6 weeks  L + H + PAC12 weeks FEC q3w x 3 → L + H 34 weeks Comparison of neoadjuvant studies: Mono HER2-targeted therapy FEC, 5-fluorouracil, epirubicin and cyclophosphamide H, trastuzumab; P, pertuzumab; T, docetaxel; L, lapatinib; PAC, paclitaxel • 1. Untch et al. SABCS 2010; Presentation S3-1 • 2. Baselga et al. SABCS 2010; Presentation S3-3

  4. GeparQuinto: Safety summary EC, epirubicin+cyclophosphamide; D, docetaxel; L, lapatinib, T, trastuzumab*Expressed as a percentage of N=310 • Untch et al. SABCS 2010; Presentation S3-1

  5. p<0.05 60 50 40 30 20 10 50.4 35.2 0 H+Ct L+Ct n = 307 308 GeparQuinto: pCR rate Patients achieving pCR (%) pCR defined as no invasive residual in breast based on central pathology report review; CI, confidence interval; Ct, chemotherapy; pCR, pathological complete response; H, trastuzumab; L, lapatinib; P, pertuzumab; T, docetaxel Untch et al. SABCS 2010; Presentation S3-1

  6. NeoALTTO: Safety summary *Includes 3 patients with Hy’s Law criteria (2 patients treated with trastuzumab and 1 patient treated with lapatinib) L, lapatinib, T, trastuzumab Baselga et al. SABCS 2010; Presentation S3-3

  7. GeparQuinto1 p<0.05 60 60 50 50 p=0.34 40 40 30 30 Patients achieving pCR (%) 20 20 10 10 50.4 35.2 0 0 H+Ct L+Ct H+Ct L+Ct n = 149 154 n = 307 308 Comparison of neoadjuvant studies: Mono HER2-targeted therapy NeoALTTO2 Patients achieving pCR (%) 29.5 24.7 For GeparQuinto pCR defined as no invasive residual in breast based on central pathology report review;for NeoALTTO pCR defined as no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen CI, confidence interval; Ct, chemotherapy; pCR, pathological complete response; H, trastuzumab; L, lapatinib; P, pertuzumab; T, docetaxel 1. Untch et al. SABCS 2010; Presentation S3-1 2. Baselga et al. SABCS 2010; Presentation S3-3

  8. NeoSphere: randomised Phase II study of neoadjuvant trastuzumab and pertuzumab TH (n=107) Trastuzumab + docetaxel FEC q3w x 3 Trastuzumab q3w cycles 5–17 S U R G E R Y Patients with operable or locally advanced /inflammatory* HER2-positive breast cancer Chemo-naïve & primary tumours >2cm (N=417) THP (n=107) Trastuzumab + docetaxel +pertuzumab FEC q3w x 3Trastuzumab q3w cycles 5–17 HP (n=107) Trastuzumab + pertuzumab Docetaxel q3w x 4→FEC q3w x 3 Trastuzumab q3w cycles 5–17 TP (n=96) Pertuzumab + docetaxel FEC q3w x 3 Trastuzumab q3w cycles 5–21 Study dosing: q3w x 4 *Locally advanced=T2–3, N2–3, M0 or T4a–c, any N, M0; operable=T2–3, N0–1, M0; inflammatory=T4d, any N, M0FEC, 5-fluorouracil, epirubicin and cyclophosphamide • Gianni et al. SABCS 2010; Presentation S3-2

  9. NeoSphere: pCR rate in ITT population p=0.0198 p=0.0141 p=0.003 60 50 40 30 Patients achieving pCR (% ± 95% CI) 20 10 45.8 16.8 24.0 29.0 0 TH THP HP TP pCR in the breast ITT, intent-to-treat; H, trastuzumab; P, pertuzumab; pCR, pathological complete response; T, docetaxel Gianni et al. SABCS 2010; Presentation S3-2

  10. NeoSphere: 10 most common grade ≥3 adverse events ALT, alanine animotransferase; LVEF, left ventricular ejection fraction H, trastuzumab; P, pertuzumab; T, docetaxel Gianni et al. SABCS 2010; Presentation S3-2

  11. Comparison of neoadjuvant studies: Combination HER2-targeted therapy Adjuvant treatment Neoadjuvant treatment S U R G E R Y TH (n=107) q3w x 4 FEC q3w x 3 H q3w cycles 5–17 THP (n=107) q3w x 4 FEC q3w x 3 H q3w cycles 5–17 NeoSphere study design1 n=417 HP (n=107) q3w x 4 T q3w x 4 → FEC q3w x 3 H q3w cycles 5–17 TP (n=96) q3w x 4 FEC q3w x 3 H q3w cycles 5–21 L 6 weeks  L + PAC 12 weeks S U R G E R Y FEC q3w x 3 → L 34 weeks NeoALTTO study design2 n=455 H 6 weeks  H + PAC 12 weeks FEC q3w x 3 → H 34 weeks L + H 6 weeks  L + H + PAC 12 weeks FEC q3w x 3 → L + H 34 weeks 1. Gianni et al. SABCS 2010; Presentation S3-22. Baselga et al. SABCS 2010; Presentation S3-3 FEC, 5-fluorouracil, epirubicin and cyclophosphamide; H, trastuzumab; P, pertuzumab; T, docetaxel; L, lapatinib; PAC, paclitaxel

  12. NeoSphere1 NeoALTTO2 60 60 50 50 40 40 30 30 20 20 10 10 0 0 TH THP H+Ct HL+Ct n = 107 107 n = 149 152 Comparison of neoadjuvant studies: Combination HER2-targeted therapy pCR rates* p=0.0141 p=0.0001 Patients achieving pCR(%) Patients achieving pCR (% ± 95% CI) 29.0 45.8 29.5 51.3 * For NeoSphere pCR in the breast; for NeoALTTO pCR defined as no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen CI, confidence interval; Ct, chemotherapy; pCR, pathological complete response; H, trastuzumab; L, lapatinib; P, pertuzumab; T, docetaxel 1. Gianni et al. SABCS 2010; Presentation S3-2 2. Baselga et al. SABCS 2010; Presentation S3-3

  13. Comparison of NeoSphere and NeoALTTO: safety • 1. Gianni et al. SABCS 2010; Presentation S3-2 • 2. Baselga et al. SABCS 2010; Presentation S3-3 Ct, chemotherapy; H, trastuzumab; L, lapatinib; P, pertuzumab; T, docetaxel

  14. Comparison of GeparQuinto and NeoALTTO: pCR* rates GeparQuinto1 NeoALTTO2 p=0.0001 p<0.05 p=0.34 60 60 50 50 40 40 Patients achieving pCR (%) Patients achieving pCR (%) 30 30 20 20 10 10 35.2 24.7 51.3 50.4 29.5 0 0 H+Ct L+Ct H+Ct L+Ct HL+Ct 307 308 n = 149 154 n = 152 * For GeparQuinto pCR defined as no invasive residual in breast based on central pathology report review; for NeoALTTO pCR defined as no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen 1. Untch et al. SABCS 2010; Presentation S3-1 2. Baselga et al. SABCS 2010; Presentation S3-3 CI, confidence interval; Ct, chemotherapy; pCR, pathological complete response; H, trastuzumab; L, lapatinib; P, pertuzumab; T, docetaxel

  15. Comparison of NeoSphere and NeoALTTO: pCR* rates NeoSphere 1 NeoALTTO2 p=0.0198 p=0.0001 p=0.003 p=0.0141 p=0.34 60 60 50 50 40 40 Patients achieving pCR (%) 30 Patients achieving pCR (% ± 95% CI) 30 20 20 10 10 24.7 51.3 45.8 16.8 24.0 29.5 29.0 0 0 H+Ct L+Ct HL+Ct TH THP HP TP 149 154 152 107 107 107 96 n = n = * For NeoSphere pCR in the breast; for NeoALTTO pCR defined as no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen 1. Gianni et al. SABCS 2010; Presentation S3-2 2. Baselga et al. SABCS 2010; Presentation S3-3 CI, confidence interval; Ct, chemotherapy; pCR, pathological complete response; H, trastuzumab; L, lapatinib; P, pertuzumab; T, docetaxel

  16. Comparison of NeoSphere and NeoALTTO: pCR* rates NeoSphere 1 NeoALTTO2 p=0.0198 p=0.0001 p=0.003 p=0.0141 p=0.34 60 60 50 50 40 40 Patients achieving pCR (%) 30 Patients achieving pCR (% ± 95% CI) 30 20 20 10 10 24.7 51.3 45.8 16.8 24.0 29.5 29.0 0 0 H+Ct L+Ct HL+Ct TH THP HP TP 149 154 152 107 107 107 96 n = n = * For NeoSphere pCR in the breast; for NeoALTTO pCR defined as no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen 1. Gianni et al. SABCS 2010; Presentation S3-2 2. Baselga et al. SABCS 2010; Presentation S3-3 CI, confidence interval; Ct, chemotherapy; pCR, pathological complete response; H, trastuzumab; L, lapatinib; P, pertuzumab; T, docetaxel

  17. GeparQuinto1 NeoSphere2 p=0.0198 p<0.05 p=0.003 p=0.0141 60 60 50 50 40 40 Patients achieving pCR (% ± 95% CI) Patients achieving pCR (%) 30 30 20 20 10 10 35.2 50.4 45.8 16.8 24.0 29.0 0 0 H+Ct L+Ct TH THP HP TP 307 308 107 107 107 96 n = Comparison of GeparQuinto, NeoSphere and NeoALTTO: pCR* rates NeoALTTO3 p=0.0001 p=0.34 60 50 40 Patients achieving pCR (%) 30 20 10 24.7 51.3 29.5 0 H+Ct L+Ct HL+Ct 154 152 149 n = n = * For GeparQuinto pCR defined as no invasive residual in breast based on central pathology report review; for NeoSphere pCR in the breast; for NeoALTTO pCR defined as no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen 1. Untch et al. SABCS 2010; Presentation S3-12. Gianni et al. SABCS 2010; Presentation S3-2 3. Baselga et al. SABCS 2010; Presentation S3-3 CI, confidence interval; Ct, chemotherapy; pCR, pathological complete response; H, trastuzumab; L, lapatinib; P, pertuzumab; T, docetaxel

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