Pertuzumab and trastuzumab combo improves efficacy for HER2-positive breast cancer

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Published: 19 Jan 2011
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Prof Luca Gianni - Istituto Nazionale Tumori, Milan, Italy

Talking to ecancertv at the 2010 San Antonio Breast Cancer Symposium, Prof Gianni explains how adding pertuzumab to trastuzumab and docetaxel eradicated tumours. Some tumours were eradicated without chemotherapy. The findings establish that the addition of pertuzumab to trastuzumab and the chemotherapy drug docetaxel has an impressive rate of tumour eradication (46 %), which is 50 % more than achieved with docetaxel and trastuzumab, the standard therapy. 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.

2010 San Antonio Breast Cancer Symposium, 8-12th December, USA

 

Interview with Professor Luca Gianni (Istituto Nazionale Tumori, Milan, Italy)

 

Pertuzumab and Trastuzumab combo improves efficacy for HER2-positive breast cancer
 

 

The press conference is about the release of the results of three trials. One is the trial that I chair and that is a joint effort and a combined effort between a non-profit organisation that is the Michelangelo Foundation based in Milan but working across all of Europe and the Roche Pharmaceuticals. What we have decided to do jointly is to exploit the neoadjuvant setting that is the clinical condition where you administer drugs before surgery to women with breast cancer to test the value of adding the new monoclonal antibody Pertuzumab directed against HER2 to the standard of therapy consisting of Docetaxel and Trastuzumab.

 

What was the method and what did you find?

 

What we found is relatively easy to say in a word and that is that addition of Pertuzumab is of benefit and is very well tolerated. There are aspects of the trial that require further definition and that is that we decided not only to compare the addition of Pertuzumab to Trastuzumab and Docetaxel but also to run one of the arms of the trial in which patients were receiving only the doublet of Trastuzumab and Pertuzumab and an additional arm where Pertuzumab and Docetaxel were given.

 

So we basically tested all possible changes in the approach due to the advent of this new monoclonal antibody. Pertuzumab, is different from Trastuzumab because in spite of the fact that it targets the external portion of the HER2 receptor, it does so in a different part of the protein and this causes the possibility of administering both monoclonal antibodies expecting additive effects.

 

In the laboratory and in animal models when you put together the two monoclonal antibodies indeed you have a synergistic activity and the mechanistic explanation for this synergy is under scrutiny now. In clinic what you observe is that the two monoclonal antibodies together in women with metastatic breast cancer are very well tolerated and that was the basis for our tests in an earlier stage of the disease – either inoperable or locally advanced breast cancer women. What we found is that indeed also in that setting we get a clear sign of at least additive efficacy at the cost of no additional toxicity.

 

One concern was that targeting the HER2 you might have a potential increase of the risk of cardiac events and for the short period of time of core administration of the two antibodies we didn’t observe any increase in the side effects.

 

What efficacy measurements did you make?

 

The efficacy was measured with the only solid endpoint that you have in the adjuvant setting and that is the pathological assessment at surgery of residual tumour. Pathological complete response means that you have eradicated the presence of invasive breast cancer in the breast. This is a very important endpoint because there is evidence from several sources and more than fifteen years of research indicating that if you eradicate the disease in the breast, those women will have an excellent disease free survival and overall survival. So it is an indirect measure of efficacy.

 

What about adverse events?

 

The side effects were mostly those of Docetaxel when you have the Docetaxel around and nothing more that we could measure. So we didn’t observe an increase in the toxicity because of the addition of Pertuzumab, while if you use the two monoclonal antibodies without Docetaxel the tolerability profile was really very, very good.

 

Should we be abandoning the basic chemotherapy?

 

The data of the NeoSphere indicated that the rate of pathological eradication with the two monoclonal antibodies without Docetaxel is 17%. That means that on one side we have a subset of women for whom there is no need for additional chemotherapy but that the larger proportion of women derive additional benefit from chemotherapy.

 

So the effort now is that of studying all the relative science and tumour bank that we have and eventually identify the biomarkers that are associated with the possibility of eradicating the tumour without chemotherapy.