1 / 9

Harold Burstein, MD Assistant Professor of Medicine Dana-Farber Cancer Institute Boston , MA

Exploring new and future standards of care in HER2 positive breast cancer: Improving efficacy in the adjuvant / neoadjuvant setting . Harold Burstein, MD Assistant Professor of Medicine Dana-Farber Cancer Institute Boston , MA. Studies of adjuvant trastuzumab therapy: Summary.

nikki
Download Presentation

Harold Burstein, MD Assistant Professor of Medicine Dana-Farber Cancer Institute Boston , MA

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. Exploring new and future standards of care in HER2 positive breast cancer: Improving efficacy in the adjuvant / neoadjuvant setting • Harold Burstein, MD • Assistant Professor of Medicine • Dana-Farber Cancer Institute • Boston, MA

  2. Studies of adjuvant trastuzumab therapy: Summary • Interim analysis of the ALLTO trial (L, T, L+T, or TL) has reported L is inferior to T in this setting; this arm has been discontinued • Romand et al, N Engl J Med. 2005;353:1673-84. • Perez et al, J ClinOncol. 2011;29:3366-73. • Piccart-Gebhart et al, N Engl J Med. 2005;353:1659-72. Smith et al, Lancet. 2007;369:29-36. Joensuu et al, N Engl J Med. 2006;354:809-20. Slamon et al, N Engl J Med. 2011;365:1273-83. http://www.alttotrials.com/patients.php

  3. 1 year of adjuvant trastuzumab appears optimal: Results from PHARE and HERA • PHARE1 • 3382 patients randomized to 6 or 12 months’ adjuvant trastuzumab, median follow-up 47.2 months • DFS 12 vs 6 months’ therapy: HR = 1.28 (95% CI, 1.05–1.56) • HERA2 • Target DFS events reached in April 2012 (725), 8 years median FU • DFS: 2 vs 1 year therapy:HR = 0.99 (95% CI, 0.85–1.14) • OS: 2 vs 1 year therapy:HR = 1.05 (95% CI, 0.86–1.28) 1. Pivot et al, Ann Oncol. 2012; 23(Suppl 9):ixe2#LBA5_PR. 2. Goldhirschet al, Ann Oncol. 2012; 23(Suppl9):ixe2#LBA6_PR.

  4. NeoALLTO– Effect of dual HER2 blockade: Study design Lapatinib 1000 mg + trastuzumab4 mg/kg  2 mg/kg(n=152) Lapatinib1500 mg (n=154) HER2 + ≥2 cm Primary endpoint:pCR R Trastuzumab 4 mg/kg  2 mg/kg(n=149) (6 weeks) Paclitaxel 80 mg/m2/wk (12 weeks) Baselga et al, Lancet. 2012;379:633-40.

  5. NeoALLTO – Effect of dual HER2 blockade: Pathologic CR pCR (%) *** ***p=0.0001 vs trastuzumab alone Baselgaet al, Lancet. 2012;379:633-40.

  6. NeoSphere – Neoadjuvant pertuzumab + trastuzumab: Study design Trastuzumab + pertuzumab + docetaxel(n=107) Trastuzumab + pertuzumab (n=107) Primary endpoint:pCR HER2 + ≥2 cm R Pertuzumab+ docetaxel(n=96) Trastuzumab + docetaxel(n=107) Docetaxel 75 mg/m2 q3w Trastuzumab 8 mg/kg  6 mg/kg Pertuzumab 840 mg/kg  420 mg/kg (4 cycles) Gianni et al, Lancet Oncol. 2012;13:25-32.

  7. NeoSphere – Neoadjuvant pertuzumab + trastuzumab: Pathologic CR pCR (%) * *p=0.0141 vstrastuzumab + docetaxel Gianni et al, Lancet Oncol. 2012;13:25-32.

  8. APHINITY: Combined HER2 inhibition with trastuzumab + pertuzumab – Study Design Anthracycline based chemotherapy Non-anthracycline based chemotherapy 6 cycles 6 cycles FOLLOW UP 10 YEARS FOLLOW UP 10 YEARS A A T T 3.4 cycles 3.4 cycles 3.4 cycles 3.4 cycles TC TC Arm 1 Arm 1 Trastuzumab* 6 mg/kg 3-weekly Trastuzumab* 6 mg/kg 3-weekly SURGERY SURGERY • Pertuzumab** 420 mg IV 3-weekly* Pertuzumab** 420 mg IV 3-weekly* Central confirmation of HER2 status Central confirmation of HER2 status R R Arm 2 Arm 2 Trastuzumab* 6 mg/kg 3-weekly Trastuzumab* 6 mg/kg 3-weekly • Placebo IV 3-weekly* • Placebo IV 3-weekly* Anti-HER2 therapy for a total of 1 year (52 weeks) Anti-HER2 therapy for a total of 1 year (52 weeks) Randomization within 7 weeks of surgery Start treatment within 1 week Randomization within 7 weeks of surgery Start treatment within 1 week Radiotherapy and/or endocrine therapy may be started after the end of adjuvant chemotherapy and in accordance with the protocol recommendations Radiotherapy and/or endocrine therapy may be started after the end of adjuvant chemotherapy and in accordance with the protocol recommendations 3-4 cycles of anthracycline containing chemotherapy 6 cycles of docetaxel + capecitabine KEY Trastuzumab A TC *Site personnel, patients, study management teams and sponsor will be blinded as to treatment assignment 3-4 cycles of taxane containing chemotherapy Pertuzumab Placebo T * Trastuzumab must be given at a 8mg/kg loading dose at the trastuzumab cycle** Pertuzumabmustbe given at a 40 mg loading dose at the first pertuzumab cycle http://www.ibcsg.org/Public/Health_Professionals/Open_Trials/IBCSG_39-11/Pages/IBCSG39-11BIG4-11_APHINITY.aspx

  9. Summary • Adjuvant trastuzumab has been demonstrated to improve DFS and OS in patients with early stage HER2 positive breast cancer • 1 year therapy appears to be optimal • Dual HER2 inhibition with lapatinib and trastuzumab in the neoadjuvant setting is superior to trastuzumab or lapatinib alone • The combination of the dimerization inhibitor pertuzumab and trastuzumab has promising activity in the neoadjuvant setting when combined with docetaxel • The APHINITY trial is addressing the role of pertuzumab in the adjuvant setting

More Related