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Extending life for women with HER2-positive MBC Andreas Makris Mount Vernon Hospital Middlesex, UK.

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Presentation on theme: "Extending life for women with HER2-positive MBC Andreas Makris Mount Vernon Hospital Middlesex, UK."— Presentation transcript:

1 Extending life for women with HER2-positive MBC Andreas Makris Mount Vernon Hospital Middlesex, UK

2 1 Yamamoto et al 2008; 2 Xu et al 2006; 3 von Minckwitz et al Schaller et al 2007; 5 Bartsch et al 2007 Herceptin + Xeloda (HX): highly active in a range of MBC settings nRR, % Median PFS, months Median OS, months 1 st line Yamamoto 1 (subgroup) *25.6 Xu NR 2 nd line or later von Minckwitz GBG *25.5 Schaller Bartsch Yamamoto 1 (subgroup) *15.8 *TTP

3 Can the efficacy of Herceptin-taxane regimens be further improved? Rationale for adding Xeloda to HT –adding Xeloda to docetaxel improves efficacy in patients unselected for HER2 status 1 Could the addition of Xeloda have the same effect in HER2-positive disease? 1 O’Shaughnessy et al 2002

4 HXT H: 8 mg/kg (loading dose), d1 followed by 6 mg/kg, d1, q3w T: 75 mg/m 2, d1 X: 950 mg/m 2 bid d1–14 CHAT trial: Herceptin plus docetaxel (HT) ± Xeloda No prior Herceptin, docetaxel or Xeloda Primary endpoint: RR Secondary endpoints: duration of response, TTP, PFS, OS, safety Stratification Prior paclitaxel Prior anthracycline Liver metastases KPS R Wardley et al 2008 HXT HT H: 8 mg/kg (loading dose), d1 followed by 6 mg/kg, d1, q3w T: 100 mg/m 2, d1

5 Case history: May year-old premenopausal woman –married with one child Cancer of the right breast –invasive ductal carcinoma (IDC) grade II, 4 cm –ER positive, PgR positive, HER2 positive (IHC 2+) –staging CT scan and bone scan normal –no comorbidities

6 Initial treatment Neoadjuvant FEC x 6 (600/60/600) –clinical PR after 2nd cycle –radiological PR after 6th cycle Wide local excision and axillary node dissection level II –22 mm, grade II, IDC, (4/9 nodes positive) Radiotherapy and tamoxifen

7 Clinical course September 2004: local relapse in breast, axillary nodes and multiple liver metastases –CT scan: numerous large lesions within the right lobe of the liver consistent with metastases –MRI scan: local breast relapse plus axillary relapse, multiple liver metastases –LVEF 60% –normal liver function tests

8 Relapse: September 2004 CT scan Multiple liver metastases MRI scan Right breast multifocal relapse MRI scan Right axillary relapse

9 Which regimen would you choose? Recap: positive HER2, ER, and PgR status; prior neoadjuvant FEC, radiotherapy, and adjuvant tamoxifen 1. Herceptin + paclitaxel 2. Herceptin + docetaxel 3. Herceptin + docetaxel + Xeloda 4. Herceptin + vinorelbine 5. Herceptin + anastrozole 6. Herceptin + Xeloda

10 Treatment choice Patient consented to CHAT trial Enrolled on 1 November 2004 –Xeloda/docetaxel stopped after six cycles –continued Herceptin Complete response in breast/axilla; PR in liver (CT scans)

11 Response in liver after enrolment in CHAT 6 months 20 months

12 CHAT: HXT significantly prolongs PFS versus HT Estimated probability Months HR95% CIp value HXT , HT Wardley et al 2008

13 Summary of CHAT: consider first-line HXT HXT is an effective first-line regimen for HER2-positive MBC HXT significantly prolonged PFS versus HT –median 5 months’ increase High RR and good tolerability Survival data immature

14 Right axilla relapse: 31 months after entry into CHAT May 2007 Relapse in the right axilla Stable disease in the liver

15 Clinical course continued At relapse → Herceptin + pertuzumab trial Herceptin and pertuzumab: – bind to different regions 1 – inhibit signalling through different mechanisms 1 – show preclinical synergy 2 1 Hubbard Scheuer et al 2006 Herceptin Pertuzumab

16 Clinical course continued Response to Herceptin + pertuzumab –after 3 months: PR in axilla; SD in liver; 1 cm lesion –at 6 months: axillary nodes normal size; liver lesion unchanged May 2008: clinically good response Total length of Herceptin therapy: 3 years, 6 months

17 Response in axillary nodes, stable disease in liver May 2007 July 2007 January 2008

18 Conclusions Xeloda + Herceptin is effective in HER2-positive disease –after Herceptin and chemotherapy –first line alone –first line with docetaxel Herceptin + pertuzumab is an active therapy at disease progression


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