The Evolution of the Breast Cancer Treatment Landscape

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EP: 1.The Evolution of the Breast Cancer Treatment Landscape

EP: 2.Updates in the Treatment of Early-stage HR+ Breast Cancer

EP: 3.Novel Agents in the Adjuvant Setting: PARP Inhibitors

EP: 4.Clinical Implications of SERENA-2 Trial Data

EP: 5.Recent Updates for the Advanced HR+ Breast Cancer Setting

EP: 6.Key Takeaways from Clinical Trials of Trastuzumab Deruxtecan in Different Populations

EP: 7.Unmet Needs for Patients with HER2+ Breast Cancer with Brain Metastases

EP: 8.The Emerging State of HER2-low Breast Cancer

EP: 9.Trastuzumab Deruxtecan in the Neoadjuvant Setting

Dr. Ian Krop: So, hello. My name is Ian Krop. I am the director of clinical cancer research at Yale Cancer Center. It's good to meet you all.

Dr. Charles Geyer: And I'm Chuck Geyer, breast medical oncologist and professor of medicine at the University of Pittsburgh Medical Center and the Hillman Cancer Center. Dr. Krop and I are going to discuss some key updates in the management of breast cancer, focusing on what was new at San Antonio, but also touching on some of the major publications earlier in the year that have had an impact.

Ian, what are some of your thoughts on how our management of breast cancer has evolved over time? I think particularly in the ER positive, HER2 negative metastatic space. To me, that's where there's been a lot of change over the past five years, and challenges, as well.

Dr. Ian Krop: Yeah, no. I think I agree that this, you know, is an area where we hadn't seen a whole lot of change in terms of, kind of, decision-making or new agents until, I guess I'm not exactly sure when TAILORx came out, but I think that, you know, really- so, I think there have been some pretty dramatic changes in- kind of, in my mind, two major areas. One is who really benefits from chemotherapy and who doesn't and we got- we had some, you know, follow up longer-term data from two key trials at San Antonio this year, and then, how do we start incorporating new agents into the early stage patient population, and we had a little bit of data there, too, but I think, why don't we start out with this- the idea of who benefits from chemotherapy. You know, we have the data from TAILORx. We had updated data at San Antonio now out, 12 years, so you know, really, you know, definitive data at that point, and some updates from RxPONDER looking at the node positive population. I mean in my mind, the data from TAILORx now, which is again, the node-negative population, looking at the intermediate Oncotype scores and showing- and looking at what the benefits of cuv- chemotherapy. You know, now we're looking at very long-term follow-up. I think the, you know, the key finding there is still that in those- in the post-menopausal patients, you know, absolutely no benefit to chemotherapy. You know, I think that- this data set really puts to rest that question now, that if people have, generally post-menopausal patients, patients over the age of 50, who have scores less than 25, you know, no benefit to chemotherapy, very similar to what we see with RxPONDER, and, you know, it's just nice to see those long term follow up data.

Dr. Charles Geyer: Do we need to give chemotherapy as well as ovarian suppression with aromatase inhibitor therapy in those pre-menopausal women with those intermediate scores on the higher end, you know. It- a challenge, I think has been in this space is that we had SOFT and TEXT being kind of done as parallel studies to these genomic studies, looking at different questions, they're both positive, so there's been a little bit of, you know, a not unexpected challenge to merge the two data sets, but I think we are coming to a point now where we're about to launch the third generation study being done with Oncotype DX. The offset study really look at those last remaining questions in the pre-menopausal women, women under the age of 50 with ER-positive, zero, one to three node breast cancer.

Dr. Ian Krop: Yeah, no, I think that that is key and I'm really happy that this, you know, study that, you know, we had- that has been kind of brewing for a while looks like it's really going to come to fruition, and just, you know, I think for our audience, who, you know, may not, kind of appreciate or have, you know- aware of this kind of nuance, you know, I think, you know, were we- the interesting finding or the one that's, as you said, you know, the kind of the perplexing finding from both RxPONDER and TAILORx was that, you know, no benefit of chemotherapy in any of the lower Oncotype scores for the women either over 50 or post-menopausal, depending on how it was defined, but yet in the pre-menopausal younger patients, we did see this benefit of chemotherapy, you know, as you got into the higher- in TAILORx, as you got into the higher scores, particularly the 21 to 25, but in RxPONDER, it seemed to be, you know, across the group, and whether that is truly a differential benefit of chemotherapy on the tumor cells in younger versus older women, or is it because of the ovarian suppression effects of chemotherapy in pre-menopausal women. You know, that's where the key question is and that's what this new study is going to address. I think, you know, at least in my per-, you know, in my view of the- all of the data, you know, if you look at the subgroups within the pre-menopausal patients, you know, many of the factors seem to support this idea that it's an ovarian suppression effect. You know, the biggest benefit is in the women from, you know, 40 to 45 who are, you know, most- who are most likely to go into menopause with chemotherapy, and have it be more premature, and, you know, a number of other factors at all would support this idea, you know, particularly in RxPONDER, where it was actually even the lowest group of Oncotype scores that benefited most from chemotherapy in the pre-menopausal patients, which, you know, would be completely counterintuitive, unless it's working off of the ovarian suppression effect, so I mean all of this data, though, is circumstantial, and we really need a definitive trial and now we're going to get it. Personally, in my clinic, I- you know, I have this discussion with my patients, with my pre-menopausal patients, bringing up the idea that much of the effect could be because of ovarian suppression, and then that would be, in my mind, a reasonable option for low oncotype score pre-menopausal women to use ovarian suppression plus endocrine therapy, rather than chemotherapy, but you still- but certainly, patients seem to be aware that we don't know that for sure, and we won't until we have this trial. I don't know how you have that discussion with your patients about this.

Dr. Charles Geyer: Yeah. I mean, for me, the- and the thing- it is important to remember with both TAILORx and RxPONDER is the large majority of the pre-menopausal receive tamoxifen as their endocrine therapy, and so we- you know, we saw SOFT and TEX, it was all about adding ovarian suppression that increased the activity, same with tamoxifen, AI took it further, so we see that improvement when you do more than tamoxifen, you know, and so for me, that still remains the real question, and why this, you know, is a lot of that benefit ovarian suppression, and clearly we don't know. I do think it is reasonable to assume a position of equipoise, and, you know, we don't know, so ideally, it would be, you know, great for community physicians who are participating in the NCTN through the groups to participate in this study that we hope to have activated by the second quarter next year, but in the absence of that, I think it's reasonable to, you know, just share with patients that we don't know for sure, that they're- that you do need more than tamoxifen. Is it chemotherapy? Is it more aggressive endocrine therapy? Is it both? This is what we are still trying to really sort out, but I think there are- there's room for options and different choices based on the data that we have.

Dr. Ian Krop: Yeah. No, I agree.