Porf. Cardoso: Thank you for the invitation to be here and explain these results to my colleagues in China. And what the group of investigators have done in the MINDACT is presented on ASCO2020， mainly the long term results of the MINDACT trial. As you probably all remember， MINDACT is a de-escalation trial. So it’s a trial that looks on how can we save chemotherapy instead of giving so much chemotherapy? And the trial was designed so that all patients had the risk of recurrence assessed by our traditional clinical pathological factors， and also by a genomic test call MammaPrint. Three situations could happen， both methods would say that the risk is low， and in that case， we would not propose chemotherapy; if all would say that the risk is high， we would propose chemotherapy; and there is a middle of this coordinate group of patients where one method says that the risk is high， and the other one says that the risk is low， now what we do is randomize， we randomize for which type of methods are we going to follow? So there is a confusion sometimes regarding MINDACT that the randomization was chemotherapy versus not， actually it was not. The randomization was between clinical factors versus genetic factors. And then we would follow what that factor would say. 

 

So as a de-escalation study， the primary endpoint of MINDACT is not a randomization， but it’s a threshold. We wanted to see that in the group of patients characterize is high risk clinically， but had mamma print low risk and randomized to follow MammaPrint and receive no chemotherapy， we wanted to see a distant metastasis free survival at five years of at least 92%. So this was the primary endpoint. In 2016， we presented the first results with a medium follow up of five years. And that result was 94.7% with a confidence interval that started at 92.5 until 96.2. Now， we have 8.7 years medium follow up. We have more than 90% of patients that have been followed by at least five years and 70% of patients have been followed by at least eight years. And what we see now is that this threshold of distant metastasis free survival at five years is now higher 95.1 with the confidence interval that starts at 93.1. And therefore， the lower boundary of the confidence interval is above 92， which was the pre-defined threshold. 

 

So this results confirm that MINDACT is a positive de-escalation trial. Very importantly， we had a secondary endpoint， and the secondary endpoint looked into the effect of chemotherapy in this group of patients with clinical high risk， mamma print low risk. What was the difference between giving and not giving chemotherapy? If you remember in 2016， this difference was 1.5%. Now with longer follow up this difference is at five years 0.9% at eight years， 2.6% with all patients confounded. Now we did an exploratory analysis looking into these results by age. What we have seen is that for women above the age of 50， so post-menopause women to give or not chemotherapy makes no difference. It’s 0.2%. But for women below the age of 50 so pre-menopause woman with luminal like cancers， ER+/HER2- clinically high but mamma print low， this difference is now 5% which we consider clinically significant. 

 

Now， why is this happening? We believe that this is not the true cytotoxic effect of chemotherapy. But it’s due to the effect of chemotherapy in suppressing the ovarian function， similar to what we see in Tailor-X. So our conclusions is that at 8.7 years medium follow up， MINDACT confirms to be a positive de-escalation study and proves the clinical utility of mamma print as a genomic tool to help us decide who need adjuvant chemotherapy， we see that in this group of clinical high， genomic low， a 2.6% difference in distant metastasis free survival for the group with chemotherapy versus no chemotherapy. In postmenopausal women. There is no difference and so you can safely avoid chemotherapy with a MammaPrint low risk， in premenopausal women we see a clinically relevant difference of 5% probably due to the chemotherapy in use of any suppression. 

 

So for pre-menopause women clinically high risk and mamma print low risk. You must discuss with the patient that there is this difference and that tamoxifen alone， it’s probably not the best treatment and that you need to add ovarian suppression or chemotherapy. Neither MINDACT nor Tailor-X help us answer this question between chemotherapy or ovarian suppression. We have to go and find this answer in other trials. The results we see are the same for lymph node negative and lymph node positive from 1-3 positive nodes. This is the summary of the results we just presented at ASCO. Thank you. 

 

Prof. Jian Zhang: That’s great. I think it’s an excellent work. Before we have three interview questions， I have one more questions for you. So do you think the ovarian suppression is very important for this kind of patients? Just you have mentioned that in premenopausal patients less than 50 years old， maybe chemotherapy induced ovarian suppression can gain the 5% of the DFS benefit. I just wonder do you have some record for this kind of patients. How many patients have been treated with OFS with HS agonists? And because the results have been published for several years. Do you have some record for these patients? 

 

Porf. Cardoso: So I remember that MINDACT enrolled almost 15 years ago. So at that time， it was rarely usage of ovarian function suppression. So the number of patients who had an ovarian suppression in MINDACT is very low in Taylor-x. So it’s about 15% that received an ovarian function suppression， most of them received tamoxifen alone. So we cannot answer this question in this trial between ovarian function suppression and chemotherapy. We have to go for maybe other trials that have looked into that question. 

 

Prof. Jian Zhang : I guess maybe you can design a new clinical trial for C-high and G-low patients randomize into two groups， The first is for the chemotherapy for premenopausal patients， and other is OFS plus AI and maybe it’s a non-inferiority clinical trials. I’m very eager for that. 

 

Prof. Jian Zhang：The first is， At this ASCO annual meeting， you reported a secondary analysis of MINDACT trial with a follow-up of 8.7 years. Compared with the first analysis in 2016， what are the DMFS and OS results of the ITT population in the chemotherapy and non chemotherapy groups of C-High / G-Low patients?

 

Porf. Cardoso : Thank you. It’s good to mention the different the end points that we analyze， just reminding everyone that the primary endpoint of MINDACT distant metastasis free survival. And this is important because it is very close to overall survival， more than disease free survival. When you look at the primary endpoint that I already explained this long term analysis make the primary endpoint even more positive， stronger with 95.1% of distant metastasis free survival at five years. When we look at the secondary question of chemotherapy versus not， we see for distant metastasis free survival， at five years， the difference is 0.9; at eight years， the difference is 2.6 for overall survival. At five years， the difference is 1.1. And at eight years 1.4. So we can say that there is a small difference， but there is a difference in distant metastasis free survival， but there is no difference in survival. So chemotherapy does not impact survival in MINDACT at least with 8.7 years follow up. 

 

Prof. Jian Zhang: Thank you. So that is an impressive a result. And we have another question for you is that you also reported the exploratory analysis of MINDACT trial at the recent SABCS conference， and got similar results with TAILORx trial， that is， people ≤50y still need to combine chemotherapy with endocrine therapy. Does age and other factors need to be considered in middle risk population? 

 

Porf. Cardoso : So I think this observations both in Tailor-X and in MINDACT， they are very interesting. But I think everyone must remember that they are exploratory analysis. They are not the primary analysis of these trials. So they are very good for us to try to understand the results. But this is not the primary question of these trials. So what these trials show both Tailor-X and MINDACT， if you have a young woman premenopausal， less than 50 years old with a clinical high risk as we define it in MINDACT and then I can explain what that means， but with a clinical high risk， you have a genomic low risk， for example， using mamma print but also using oncotype. In that case， the benefit of giving chemotherapy or not becomes clinically significant. However， most of us believe that is because these women become because of chemotherapy. And so we believe that if these women had been treated with tamoxifen plus ovarian suppression， or AI plus ovarian suppression， we would not see that difference， but we cannot prove it， not with Tailor-x and not with MINDACT. We would need to do the trial that you suggested that I wish we had financial support to run that trail. 

 

Prof. Jian Zhang: OK， that’s great， so another the last question is that In the study of MINDACT and TAILORx， the majority of patients’ endocrine therapy was TAM alone. For younger patients under 50 years old， should the benefits come from combination of chemotherapy or OFS?  

 

Porf. Cardoso : So as I just mentioned， we cannot conclude that from the MINDACT or the Tailor-x we cannot answer that question. Is it an ovarian suppression or is it chemotherapy? But my personal opinion is that it’s due to the ovarian suppression. And so in these women that have a clinical high risk and you perform a mamma print and is low risk， I would treat them with in the endocrine therapy plus an OFS. 

 

Prof. Jian Zhang : That’s great. I just want to ask another question that do you divide the patients less than 50 years old into two or three groups just to less than 35 or 40 and another is 40-50. Because we know the OFS is very important for patients less than 40 years old， maybe chemotherapy induced ovarian suppression is more important in this kind of population. So do you have any results to show us？ 

 

Porf. Cardoso : That’s a very good question. The problem is that we have very small number of patients below the age of 40， very few patients that were included in MINDACT and also very few in Taylor-x. So for those very young patients， we cannot provide an answer. But if we look between the 40 to 45 and then 45 to 50， indeed， you see that this effect is mostly on the 45 to 50， so exactly on those where chemotherapy is more likely to induce menopause. So you’re right. It is linked to the age. It’s just that for the very young， we do not have enough patients to conclude that. But for above 40 and above 45， we can see that difference.

 

Prof. Jian Zhang : Okay， thank you very much for your presentation and answers. I think this is a very impressive and interesting clinical trail result. I think maybe in the near future for five years to 10 years， maybe we could not find another interesting trial impress me. Again thank you very much!