The combination of pertuzumab (Omnitarg, Genentech) and trastuzumab (Herceptin, Genentech) had superior antitumor activity in women with early HER2-positive breast cancer, according to Phase II study results of the NeoSphere neoadjuvant trial.Details of these study results were presented at the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 8-12, 2010.

Pertuzumab is a monoclonal antibody. It is the first of its class in a line of agents called HER dimerization inhibitors. By binding to HER2, it inhibits the dimerization or pairing of HER2 with other HER receptors, which is hypothesized to result in slowed tumor growth. Pertuzumab is the first investigational medicine designed to specifically prevent the HER2 receptor from pairing with other HER receptors (EGFR/HER1, HER2, HER3, HER4). In cancer cells, interfering with HER2’s ability to collaborate with other HER family receptors blocks cell signaling, which may ultimately inhibit cancer cell growth or lead to the death of the cancer cell.

The modes of action of pertuzumab and trastuzumab are believed to complement each other. Both bind to the HER2 receptor but in different regions. By doing so it is hypothesized that the two antibodies in combination may provide a more comprehensive blockade of the HER signaling pathways than either agent alone.

?The findings establish that the addition of pertuzumab to trastuzumab and the chemotherapy drug docetaxel has an impressive rate of tumor eradication (46%), which is 50% more than achieved with docetaxel and trastuzumab, the standard therapy,? said Luca Gianni, M.D., director of medical oncology at the Fondazione IRCCS Istituto Tumori di Milano.

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?In addition, the combination of trastuzumab and pertuzumab without chemotherapy is capable of eradicating the tumor in a remarkable fraction of cases (17%) without any of the toxicities commonly seen with chemotherapy,? Gianni said.

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NeoSphere is a randomized trial that tested the efficacy of the new HER2-directed monoclonal antibody pertuzumab in combination with trastuzumab with or without chemotherapy. The trial included 417 women; all participants received four cycles of therapy before they underwent surgery, or as neoadjuvant therapy.

The results showed that combining pertuzumab with trastuzumab might offer improved efficacy to women with early HER2-positive breast cancer, according to Gianni. Additionally, a small percentage of tumors could be treated and eventually cured without chemotherapy.

?The most important result of the study is that a relatively small neoadjuvant trial of short duration can rapidly provide data that better outline the value of different new strategies and shape the approach to further and much larger adjuvant studies,? Gianni said.

Investigators are working on a follow-up, adjuvant randomized trial with pertuzumab added to trastuzumab and chemotherapy. They are also conducting several molecular analyses aimed at improving the ability to predict benefit or failure and permit greater focus on personalized treatment of HER2-positive breast cancer.

Commenting on the trial results, Hal Barron, M.D., executive vice president, Product Development and chief medical officerat Genetech said “We are committed to developing new medicines that make a difference for people living with cancer and to advancing personalized treatments. The clinical data presented today (at SABCS) add to the body of evidence that this novel targeted regimen plus chemotherapy may improve outcomes in women with HER2-positive breast cancer.”

Based on these findings, Genentech plans to initiate a Phase III study in HER2-positive early (adjuvant) breast cancer in 2011. In addition, CLEOPATRA, a Phase III study evaluating the efficacy and safety profile of pertuzumab and trastuzumab plus chemotherapy as a first-line regimen in people with HER2-positive metastatic breast cancer, completed enrollment in Q2 2010 and results are expected by the end of 2011.

For more information:
Gianni L, Pienkowski T, Im Y-H, Roman L, Tseng L-M, et al [S3-2] Neoadjuvant Pertuzumab (P) and Trastuzumab (H): Antitumor and Safety Analysis of a Randomized Phase II Study (‘NeoSphere’). Friday, December 10, 2010 – 9:45 AM General Session 3 (9:30 AM-11:30 AM) 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium.

Photo by ? SABCS/Todd Buchanan 2010

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