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Old 01-08-2009, 03:55 PM   #1
eric
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Pertuzumab May Re-sensitize Cells to Herceptin

http://professional.cancerconsultant....aspx?id=43050
Researchers from Spain and the United States presented a review of data from two Phase II trials evaluating pertuzumab that demonstrated the synergistic potential between pertuzumab and Herceptin® (trastuzumab) among HER2-positive breast cancer patients who progress on Herceptin therapy. These data were presented at the 2008 annual San Antonio Breast Cancer Symposium on December 10-14, 2008.[1]
Pertuzumab is a recombinant humanized monoclonal antibody (2C4) that binds to the extracellular domain II of the HER-2 receptor. Through its binding, it blocks the ability of dimerization between HER2 receptors and other receptors of the HER family. Pertuzumab is referred to as a HER dimerization inhibitor, or HDI. Pertuzumab binds at different positions on the HER2 receptor from Herceptin, blocking the pathway through different mechanisms. Phase I and II trials have both demonstrated synergy between pertuzumab and Herceptin, with the addition of pertuzumab to Herceptin providing responses among women who progressed following prior Herceptin therapy. The Phase III trial evaluating pertuzumab, referred to as the CLEOPATRA (Clinical Evaluation Of Pertuzumab And TRAstuzumab) trial, is a randomized, double-blind, placebo-controlled trial comparing pertuzumab, Herceptin, and chemotherapy to Herceptin and chemotherapy in previously untreated HER2-positive, metastatic breast cancer; this trial is being conducted in 18 countries.
The first Phase II study evaluating pertuzumab included 66 patients with HER2-positive, metastatic breast cancer who had progressed on prior therapy with Herceptin.[2] Patients received Herceptin (4 mg/kg loading dose plus 2. mg/kg weekly or 8 mg/kg loading dose and 6 mg/kg every three weeks) plus pertuzumab (840 mg loading dose and 420 mg every three weeks).
  • Overall responses were achieved in 24% of patients (7.6% complete response [CR] and 16.7% partial response [PR]).
  • Disease stabilization for at least six months was achieved in nearly 26% of patients.
  • Three patients experienced grade 3 adverse events, which were all resolved.
  • No patients experienced grade 4 adverse events or symptomatic left ventricular ejection fraction (LVEF) declines.
The second Phase II trial included 11 patients with HER2-positive, metastatic breast cancer who had progressed on Herceptin.[3] Patients received Herceptin (8 mg/kg loading dose followed by 6 mg/kg every three weeks) plus pertuzumab (840 mg loading dose followed by 420 mg every three weeks).
  • Overall responses were achieved in 18% of patients (all PR).
  • Disease stabilization for at least 18 weeks was achieved in 27% of patients.
  • There were no treatment-limiting adverse events.
  • Grade 1-3 left ventricular systolic dysfunction (LVSD) occurred in 45% of patients, all of whom had previously received at least 240 mg/m2 Adriamycin® (doxorubicin). Of these patients, 60% had resolution of LVSD following therapy.
  • All other adverse events were mild to moderate in nature.
These researchers stated, “This is a promising biologic combination therapy targeting HER2 disease that shows activity while avoiding typical chemotherapy side effects.” A Phase III trial will randomly allocate 800 patients with metastatic breast cancer to Herceptin plus chemotherapy or Herceptin plus chemotherapy plus pertuzumab.
Comments: These are interesting data that could result in increased effectiveness of Herceptin.

References:

[1]Baselga J, Imadalou K, Paton V, Gray D, Swain S. Efficacy, safety, and tolerability of dual monoclonal antibody therapy with pertuzumab + trastuzumab in HER2+ metastatic breast cancer patients previously treated with trastuzumab. Program and abstracts of the 31st Annual San Antonio Breast Cancer Symposium; December 10-14, 2008; San Antonio, Texas. Abstract 3138.
[2] Gelmon KA, Fumoleau P, Verma S, et al. Results of a phase II trial of trastuzumab (H) and pertuzumab (P) in patients (pts) with HER2-positive metastatic breast cancer (MBC) who had progressed during trastuzumab therapy. Program and abstracts of the 44th American Society of Clinical Oncology Annual Meeting; May 30-June 3, 2008; Chicago, Illinois. Abstract 1026.

[3] Portera C, Walshe J, Rosing D, et al. Cardiac toxicity and efficacy of trastuzumab combined with pertuzumab in patients with [corrected] human epidermal growth factor receptor 2-positive metastatic breast cancer. Clinical Cancer Research. 2008;14:2710-2716.
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Old 01-11-2009, 05:06 PM   #2
Laurel
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Join Date: May 2008
Location: Hershey, PA. Live The Sweet Life!
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This is amazing! Yippee!
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Smile On!
Laurel


Dx'd w/multifocal DCIS/IDS 3/08
7mm invasive component
Partial mast. 5/08
Stage 1b, ER 80%, PR 90%, HER-2 6.9 on FISH
0/5 nodes
4 AC, 4 TH finished 9/08
Herceptin every 3 weeks. Finished 7/09
Tamoxifen 10/08. Switched to Femara 8/09
Bilat SPM w/reconstruction 10/08
Clinical Trial w/Clondronate 12/08
Stopped Clondronate--too hard on my gizzard!
Switched back to Tamoxifen due to tendon pain from Femara

15 Years NED
I think I just might hang around awhile....

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