We conducted a randomised double blind clinical trial comparing trastuzumab and chemotherapy, the original trastuzumab versus a biosimilar called CTP6 plus chemotherapy in patients with early stage breast cancer, stage 1, 2, 3 breast cancer. We found that both the safety and the efficacy were basically not exactly the same but very similar within the boundaries, pre-specified boundaries, in terms of pathologic complete response. The primary endpoint of the trial was pathologic complete response meaning eradication of breast cancer in the breast and the axilla, the axillary lymph nodes, and again the PCR rates were very similar. In terms of safety also we had done previously a pharmacokinetic study showing that the levels of trastuzumab were very similar between the two drugs and in this large randomised trial with more than 500 patients also we showed both the PK safety and efficacy are very similar.
I suppose the question is who should be using biosimilars and if not everyone why not?
Biosimilars are not approved by the FDA yet, therapeutic biosimilars. Therapeutic monoclonal antibodies are not approved by the FDA, only GCSF which is a supportive care biosimilar is approved. So as soon as any of these biosimilars meet all the regulatory requirements to be approved by the FDA or the EMA and other regulatory agencies they will be used instead of the original trastuzumab. There are differences in terms of regulatory pathways so to get an original monoclonal antibody approved of course the sponsor has to do many clinical trials; for biosimilars it isn’t clear because none of them are approved. But there is likely to be extrapolation from a clinical trial showing similar safety and efficacy to other types of indications or situations so there will not be a trial for each of those indications. At the same time the penetrance or the use of these biosimilars once they are approved is yet to be seen. The main advantage, of course, is that it will reduce the cost of the original monoclonal antibodies which hopefully will play a big impact, not only in the US but globally, where some patients may not have access to these types of drugs. This way hopefully when we have more than one biosimilar and there is really competition the cost will go down.
In terms of trastuzumab monoclonal antibody therapy the main issue is in what setting should these biosimilars be studied, whether it’s in early stage breast cancer or metastatic breast cancer. We chose to do a randomised trial in the neoadjuvant setting in patients with early stage breast cancer; other biosimilars are being studied in patients with more advanced metastatic breast cancer. In my opinion the neoadjuvant setting is a better system or model to study these types of therapies because the population is more homogeneous, they have not been exposed to other therapies in the past, they are not extensive disease with all the symptoms and so on. So in my opinion doing the studies in early stage breast cancer is more reassuring that these therapies will work and then it’s easier to extrapolate to patients with metastases as opposed to having studies in metastatic disease and then are we going to extrapolate to early stage breast cancer? Of course if you have both it’s ideal but this is one of the decisions we made with this particular company using the CTP6 antibody to study in the neoadjuvant setting.
At ASCO at the same session there was another antibody, another biosimilar, called SB3 from another company. They were both discussed at the poster discussion session. The other one also, SB3, showed similar pathologic complete responses compared to the original trastuzumab so there seems to be a movement towards this type of testing in more early stage, HER2 positive breast cancer.