ML: Hello dear colleagues, welcome to this ecancer expert meeting. We are privileged to be here with Professor Virginia Kaklamani to discuss about the most important data from the San Antonio Breast Cancer Symposium 2024 and particularly focussing on genomic testing. My name is Matteo Lambertini, I’m a medical oncologist and professor in medical oncology at the University of Genoa San Matino Hospital in Genoa, Italy. We have the Director of the San Antonio Breast Cancer Symposium with us, Professor Kaklamani, who is a professor of medicine in the division of haematology, medical oncology at the University of Texas Health Science Center in San Antonio and the leader of the breast cancer programme at the Mays Cancer Center in San Antonio. So thanks a lot, Virginia, for being with us today.
VK: Thank you, Matteo, it’s a pleasure.
ML: So today we are going to discuss mostly genomic data and I would like to focus mostly on two important presentations in General Session 3, starting with the first one which is probably the most provoking one for our clinical practice which is a post-hoc analysis of the TAILORx trial. Just a reminder that the TAILORx was a study that was stratifying patients with node negative disease based on their recurrence score with Oncotype DX to receive endocrine therapy alone, chemotherapy plus endocrine therapy or be randomised to endocrine therapy with or without prior chemotherapy. So those patients with a recurrence score less than 11, so 0-10, endocrine therapy alone; 11-25 randomised to receive or not chemotherapy; then those with a high recurrence score, so 26 or higher, were receiving chemotherapy plus endocrine therapy.
Here at the San Antonio Breast Cancer Symposium the TAILORx investigator presented the post-hoc analysis including 5,249 patients that received anthracycline taxane-based chemotherapy or TC, docetaxel cyclophosphamide, before receiving endocrine therapy. Most of these patients were in the high recurrence score, so 26-100, or some patients in the cohort recurrence score between 11-25. Out of these 2,500 patients most of them, more than 2,000, received the TC regimen and slightly less than 500 received anthracycline plus taxane-based chemotherapy, dose dense or standard duration, or concurrent [TC] regimen. When looking at characteristics, this was not a randomisation so this was per physician’s choice and, as expected, there was a tendency for those patients receiving also anthracycline on top of taxane-based chemotherapy to have maybe a higher grade tumour, higher recurrence score, and to be more premenopausal women, maybe lower expression of hormone receptors.
But the most, I would say, provoking data that were presented are the distant recurrence free interval data at five years based on the recurrence score, looking at the population of patients that received TC versus anthracycline plus taxane-based therapy. Apparently what the authors have shown is that in those women with a recurrence score less than 31 there is apparently no difference between TC and anthracycline plus taxane-based chemotherapy with a very good survival rate at five years. For those patients with a recurrence score of 31 or higher there is around a 5% difference in distant recurrence free interval favouring the anthracycline plus taxane-based chemotherapy versus the TC regimen. Similar findings also in distant relapse free survival and overall survival for the cohort of patients with a recurrence score of 31 or more with Oncotype DX.
At a subgroup analysis this benefit appeared to be mostly observed in patients with larger tumours, meaning a tumour size more than 2cm. It was a bit less clear for those having a tumour size less than 2cm. There was a tendency for a larger benefit in the premenopausal as compared to the postmenopausal patient population. The final important result presented is that, apparently, the higher the recurrence score, the larger the expected benefit of anthracycline plus taxane-based chemotherapy versus the TC regimen. So before going into a few questions that I would love to ask, Virginia, what’s your overall take on this study?
VK: This is extremely clinically useful because we have this question, and we’ve had it for a long time, can we use a genomic risk not to decide just whether to give chemotherapy or not but what kind of chemotherapy. I’ve always said we don’t have any data so the genomic risk should be used just to make a decision on chemotherapy and now we do have data that suggests that it can also be used to decide what kind of regimen to use. So, to me, very, very clinically useful and I’ve already changed my practice based on these results.
ML: Maybe the first question on clinical practice, and this was also asked in the audience, we are in an era in which we are trying to move away from anthracyclines as much as we can in different disease subtypes, trying to stratify better the risk of recurrence of the patient to decide if to give anthracycline or not. But, based on this data, would you give anthracyclines plus taxane-based chemotherapy to all patients with hormone receptor positive, HER2 negative, node negative disease, with a recurrence score more than 31, meaning even a 1.5cm tumour or 22cm tumour node negative?
VK: This is the important thing because TAILORx was done in the node negative patient population where, as you have alluded to, we typically don’t use an anthracycline. We have data from PlanB, we have data from the ABC trials, both of them suggesting that in ER positive patients the anthracyclines don’t really benefit patients. But what we’re seeing in all of these trials is that the higher the risk, that’s where the usefulness of an anthracycline kind of creeps in and I think this is what we’re seeing here as well. So, to quickly answer your question, yes I will.
ML: Maybe something that I may have missed in the presentation, if you know it, for the TC regimen it was specified it works for four cycles or six cycles or this was not collected which somehow could be important to interpret the results.
VK: It would be very important because, as you know, both the ABC and the PlanB were using six cycles of TC. Now, in the US we don’t do six cycles and since this was a US study I would assume the majority, if not all, patients received TC four but they didn’t mention that in their presentation. That would be one of the important things to look at. Another one is they decided to get 31-100 but they have patients receiving chemotherapy from 26-30. I’m sure they did analyses including or excluding these patients, it would be nice to see them to really understand why that 31 was chosen as the cut-off for use of anthracycline.
ML: I fully agree. Maybe just a final quick question before moving to the second presentation on also the data based on menopausal status was quite interesting to me. The benefit seems to be larger in premenopausal women but then this goes back again to the recurrent question on the chemoendocrine effect. So potentially anthracycline plus taxane-based therapy versus four cycles of TC is probably more toxic so how to interpret also this part of the data.
VK: To me, and I think the presenter made that comment that because we saw benefit both in pre- and in postmenopausal patients it didn’t seem to be a menopausal effect which is what we would have assumed without that analysis. Now, as you mentioned, the benefit in postmenopausal patients was lower, the p-value was still statistically significant so I feel relatively reassured, even though this is a post-hoc analysis. Now, one thing that is important and we should mention, and you asked that question to me, the tumour size. Because there were patients, there was an analysis looking at tumour size more than 2cm or less than 2cm. The tumours more than 2cm had more benefit from the anthracycline than the smaller tumours although there were fewer patients in that smaller tumour group. So, again, unclear what to do with that data. There still seemed to be a benefit from the anthracycline but maybe use a little bit of caution in that patient population.
ML: Yes, I agree on that. I will still consider the clinical risk together with the genomic risk to decide maybe on the chemotherapy, especially for the T1/N0, N0 high genomic risk. But, yes, I definitely agree that these are useful data from a clinical perspective. If you agree I will move to the second presentation in the same general session – an updated analysis from the ADAPT hormone receptor positive, HER2 negative trial.
This is a German study, an important academic effort with a complicated design but a very elegant one. So this study has been already reported in JCO as well as in Annals of Oncology a couple of years ago; included more than 5,600 patients with hormone receptor positive, HER2 negative disease and criteria for being candidates for adjuvant or neoadjuvant chemotherapy. Patients were exposed to a short window of endocrine therapy, 3-4 weeks, they were tested with Oncotype DX at baseline, Ki67 centrally tested. Then, after these 3-4 weeks of endocrine therapy, they received surgery or biopsy and Ki67 was assessed centrally again to look into the endocrine response that was defined as having Ki67 of 10% or less after these 3-4 weeks of endocrine therapy. Then patients were divided into two groups – the low/intermediate-risk group and the high-risk group. For the low/intermediate-risk group, meaning patients with node negative or N1, so 1-3 positive nodes, including patients with a recurrence score less than 12 or those with a recurrence score between 12-25 and with endocrine response, so a drop in Ki67 after neoadjuvant treatment, all these patients received endocrine therapy alone and they had very good, very excellent survival outcomes reported in JCO a couple of years ago.
The second group of patients is the high-risk group, meaning patients patients with N2/N3 disease, 4 or more positive nodes, and within the group of N0/N1 cohort the high-risk group included patients with a recurrence score of 26 or more and those with a recurrence score between 12-25 without endocrine response, so with Ki67 that was higher than 10% after the short course of endocrine therapy before biopsy or before surgery. This cohort of high risk patients was randomised to two different chemotherapy regimens – an anthracycline/taxane-based regimen but the randomisation was between paclitaxel 175mg/m2 given every two weeks, so in a dose dense fashion for four cycles versus eight cycles of weekly nab-paclitaxel. So this was the randomisation and all patients received four extra cycles of dose dense epirubicin and cyclophosphamide.
So the authors here at the San Antonio Breast Cancer Symposium have looked into the survival outcomes from this study. They reported last year in Annals of Oncology the pCR rate for the neoadjuvant group showing that nab-paclitaxel appeared to perform better than paclitaxel in this group of patients – almost a doubling in the pCR rate with nab-paclitaxel versus paclitaxel. However, based on the data presented in San Antonio the long-term outcomes, including all patients receiving chemotherapy, so not only the neoadjuvant cohort but also those that received the treatment adjuvantly, which is around 2,000 patients overall, there was no difference between the two treatment regimens, there was just a signal of a tendency for better disease free survival for the nab-paclitaxel cohort in terms of disease free survival in the order of 3% absolute difference but overall the study did not show differences in most of the survival outcomes. The conclusion of the authors was that we could consider potential nab-paclitaxel as an alternative to standard paclitaxel in this setting, based also on the toxicity profile that appears to be similar with just a little bit more grade 3 haematological events for nab-paclitaxel. So in terms of how to interpret this data, first of all I’m going to ask Virginia just to comment on this complex analysis. Also considering the other data we had from the [ 13:41] and the ETNA trial on nab-paclitaxel in early breast cancer which is controversial.
VK: Overall you can say that nab-paclitaxel may be a tiny little bit better but overall relatively similar to paclitaxel. So I don’t think with all of these studies that we have now in the adjuvant setting with nab-paclitaxel, I don’t think that it’s clearly a winner compared to paclitaxel. As you mentioned, toxicity profile relatively similar, a little different in different toxicities but when you look at all of them together you’re getting relatively similar toxicity. So I personally don’t use nab-paclitaxel unless somebody has an allergic reaction or some intolerance to paclitaxel and then I’m gladly switching them to nab-paclitaxel for the remainder of their treatment.
ML: The same practice here, maybe just a question on the paclitaxel because here they’ve used in the standard arm paclitaxel 175 mg/m2 in a dose dense manner as was used, for example, in the GAIN-2 trial a few years ago. In your practice do you prefer weekly paclitaxel or this dose-dense 175 mg/m2 paclitaxel regimen?
VK: I usually use the dose-dense 175 mg/m2, I find it much easier for my patients. Coming in weekly for 12 weeks tends to be pretty hard so every two weeks just for four cycles tends to be much easier, well tolerated, so that’s what I use. We had updated results from the SWOG trial as well looking at q2 weeks versus weekly and they were equivalent.
ML: Thanks for that. Maybe just a final comment on this study. It has been a very important platform to launch the super-important ADAPTcycle trial which is the next step, it’s what actually we are all very much looking forward to, the possibility to spare chemotherapy to some patients with high-risk disease that may potentially benefit from the addition of a CDK4/6 inhibitor. So we may reinforce the endocrine therapy in a subgroup of these patients to try to avoid chemotherapy. The trial has completed accrual so we hope to see it in San Antonio maybe in a few years, I don’t know the follow-up, how is that, but I think it’s going to be on the stage at San Antonio at some point.
VK: I agree, that will be really important for us to see whether we can use a CDK4/6 inhibitor instead of chemotherapy for these high-risk patients as we’re all trying to move away from chemotherapy and then we have studies suggesting some benefit. We can’t help feel that we should be doing more for our patients.
ML: And we are almost at the end of the session. Maybe just a general comment on the other abstracts and poster presentations on genomic testing in breast cancer. There have been a lot of real-world studies presented at the San Antonio Breast Cancer Conference. To me, the main take is that the genomic tests are helpful to avoid chemotherapy for many patients that actually were candidates for chemotherapy before the availability of these results. Across different populations and different countries the prognostic value of these tests remains quite significant and quite important. There have been a lot of studies on that. I don’t know, Virginia, if you have something to mention on this point?
VK: The reason we use these tests in clinic every day is because they really help inform us what to do with our patients. It’s really been a revolution in breast medical oncology, all of these genomic assays. So we’re grateful for all of these large studies that have taken not only a lot of effort from us but also many, many, many patients – you mentioned TAILORx, more than 10,000 women randomised on this trial. So it’s an absolutely unbelievable effort.
ML: Thanks a lot, Virginia, it has been as always very nice discussing with you and thanks also for organising such an exciting congress. This year has been even better than the prior year which is always very difficult to make it even better but thanks for that. I think we were all very excited at the end of the week. Finally, I wanted to thank ecancer for giving us this opportunity and you all for listening. Thanks a lot. Ciao.
