Treatment decision guided by CTC count may improve long-term outcomes for mBC

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Published: 9 Dec 2022
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Prof Jean-Yves Pierga - Institut Curie, Paris, France

Prof Jean-Yves Pierga speaks to ecancer as part of SABCS 2022 about a study looking at circulating tumour cells-driven choice of first line therapy for ER positive HER2 negative metastatic breast cancer.

He explains that patients were randomised between two arms. In the first arm the treatment was decided by the level of CTC in the blood and in the second arm the treatment was decided by clinical evaluation by the clinician.

Prof Pierga reports that findings focused on a group of patients where there was a discordance between the clinicians evaluation and the CTC count. In this group the patients in the CTC arm were treated with chemotherapy and had a favourable overall survival compared to the second arm where patients were treated with hormonal therapy.

The study is STIC METABREAST which was presented by my colleague, François-Clément Bidard from the Curie Institute, aiming to demonstrate the clinical utility of circulating tumour cells in the management of metastatic breast cancer. The idea is for several years now we know that detection and enumeration of circulating tumour cells is associated with prognosis in metastatic breast cancer. However, we don’t have the clear evidence that having this information can help the patient management and there is no clear demonstration of the clinical utility of CTCs in the management of breast cancer.

So the aim of this study was to use this information about the prognosis of the patient to help the clinician to decide which type of treatment they should use in first-line metastatic breast cancer patients with hormone receptor positive and HER2 negative disease. So the idea at that time was to decide between starting the treatment with hormonal treatment, as it is the recommendation for these patients in general, or to start with chemotherapy because the disease seems to be quite aggressive and the aim was to obtain a clinical response.

So it was a randomised trial which included less than 800 metastatic breast cancer patients in first line. It was run all over France. The patients were randomised between having in all cases circulating tumour cells detected in the blood, so that was the case for all the patients, and then they were randomised between having the information of the CTC count given to the clinician or doing the treatment and choosing the treatment between hormonal treatment and chemotherapy according to the clinical evaluation by the physician. In the arm where the patient had the information about the levels of CTCs, when the level was high the recommendation was to give chemotherapy and when the level was low the recommendation was to give hormonal treatment.

The first conclusion of this trial and which was the primary aim of the study was to show that the two arms were equivalent in terms of progression free survival and overall survival. So that showed that clearly using just one parameter, which was CTC level, was doing as well as clinical feeling or evaluation by the physician to decide between hormonal treatment or chemotherapy for a patient. However, what was presented at this meeting this year was the update of the trial. What was observed was the behaviour of the different groups of patients. We had a group of patients in this study who had a clinical evaluation showing that the disease was of good prognosis, we would call them clinical low, and which was correlated also with a low level of CTC. So this category of patient which we presented, nearly 48% of all the population of the clinical trial, had quite a good outcome with overall survival around five years with only monotherapy of hormonal treatment. On the other hand, we had a group of patients with high levels of CTC, so we’d call them CTC high, and a clinical evaluation of aggressive disease, so a clinical high. This group of patients, which was a small group of patients, nearly 13% of the patients, had a poor prognosis with a low overall survival.

In the middle we had a group of patients with discordant evaluation and specifically the group of patients with clinical evaluation of a favourable evolution of the disease, so we call them clinical low. So according to the physician the disease was not aggressive but we had the information that in this group of patients the level of CTC was high. So there was this discordance. So according to the protocol there were some patients in this situation who received chemotherapy and another part of this group of patients who received only hormonal treatment.  So this group of patients represented around 25%, a quarter, of the population.

What we observed clearly that in this group of patients there was a clear benefit of receiving chemotherapy compared to hormonal treatment. The update of the trial clearly demonstrated that there was also a superior clinically significant benefit in terms of overall survival in this group of patients receiving chemotherapy because their CTCs were high but the appearance of the disease clinically was favourable. So that was the main result of this study, showing that using CTC you could make a better decision for the patients in terms of strategy.

However, now the standard of treatment in first line for metastatic hormone receptor positive disease is to use a combination of CDK inhibitors and hormonal treatment. So we cannot say now that using CTC would be clearly useful in this situation and we will not change the new standard of treatment. So the clinical utility now with the new strategy which is used in general for this disease is no more of clear interest now. However, what we can say now is that the challenge of the discussion between and the choice between chemotherapy or a new treatment like antibody-drug conjugates that could be used in this population or to challenge the patient with the disease with a new hormonal treatment and specifically now with the SERDs, so this oestrogen receptor degrader, the first one is fulvestrant but there are new SERDs developed with some clinical evidence of benefit for the patient, can be used and some of them are used in monotherapy. So that could be an important field for the use of CTCs, use them, for example, to help to decide between starting after progression after the first line, including a CDK inhibitor, what should we do – should we re-challenge with another hormonal treatment or should we go directly to chemotherapy or maybe in a few years ADC. So we clearly believe that that could be a clinical utility for the CTC, to use them in this type of situation for the patient.

So, in conclusion, with the design of the study, and it was a discussion by Professor Dan Hayes was a discussant of this presentation, who clearly said we are nearly there for the demonstration of the clinical utility of CDC and with a high level of evidence because it was a prospective trial but not clearly in first line but maybe in the other line where we need to have a new biomarker to decide which patients will clearly benefit of less aggressive treatment like hormonal treatment of new generation or to go directly to chemotherapy because the disease is clearly aggressive and there will be rapid progression of the disease.

So that would be what I could say about this STIC METABREAST study and we think that there is still a lot of interest in the development of the use of CTC in the management of metastatic disease.

This study was run supported by an academic grant from the French Government and several centres in France participated in this study. It’s also in the field of a society which is the European Liquid Biopsy Society which is also involved and several investigators are part of this society.