SABCS 2024 Highlights - EUROPA, TAILORx, PADMA, EMBER-3 with Dr. Jame Abraham

Intro Welcome back to another episode of the Oncology Brothers Podcast. I'm Rahul Ghosane, and with me is my brother and Co host Rohit Ghosane. Today we have the pleasure of speaking with Doctor Jane Abraham from the Cleveland Clinic to discuss some key abstracts and hormone receptor positive space from the San Antonio Breast Cancer Symposium 2024. Doctor Abraham, thank you so much for joining us today. Speaker 2 Thank you Rahul and Rohit for including me in this conversation. I appreciate your effort to educate the community on the new developments from San Antonio Breast Cancer. Speaker 3 James, thanks so much for joining us today and very much appreciate the kind words. Let's dive into hormone receptor space from San Antonio Breast Cancer Symposium or next 15 to 20 minutes. We are hoping to cover 4 important studies, 2 from early stage, which will be Europa and then update from Taylor Rex and then two from metastatic space, Padma and Amber 3. OK, let's start off with our first study, Europa trial. Europa Trial This study looked at endocrine therapy versus radiation therapy in early stage breast cancer. Could you please walk us through the study design and how these results are impacting your practice today? Speaker 2 The Europa trial is an interesting study right now because this is something we face now clinic on a day-to-day basis. It's a phase three trial of about 926 patients. Patients are older than 70 who underwent a breast conservation surgery with or without central node biopsy, small tubers, T1N0, ERPR more than 10% and with a low Ki 67 and less than 20%. So they are asking the question of radiation treatment by itself versus endocrine treatment by itself in adjuvant setting. And the primary endpoint is an ipsilateral breast cancer recurrence and quality of life. And of course they looked at the secondary endpoints, local regional occurrence, breast cancer specific survival rate etcetera. So in the interim analysis, what they found was that radiation therapy offers better quality of life than endocrine treatment and then lower incidence of treatment related AES in the ARTEA. And at this point, there's no safety signal, there's no safety concerns. Speaker 1 As you brought up, this is a common thing that we run into in this particular patient population. But the primary endpoint of looking at epsilateral recurrence, often when we're talking about endocrine therapy, we're also talking about decreased risk of contralateral. We're talking about decreased risk of distance disease here as well based on this study. Jane, is this going to change your practice or you're waiting on long term data? Speaker 2 I think we should wait for long term data to apply this broadly. But and I when I talked to this particular patient who has joint pain and I sure she already has tried this, then I can say if you want to choose one versus the other, RT is fairly safe. And then because of what we just talked about and if you want to omit and treatment, it's not completely unreasonable. But of course, it's a risk benefit, individualized shared decision making. Speaker 1 Absolutely. It was so exciting to see that this SABCS. We saw quite a few studies trying to focus on de escalation and ensuring that less is perhaps more. And this was one of the studies. OK, while we're talk talking about early breast cancer, this is a good segue to our next study, Tiller X study. Tiller X Study Tiller X has been practice changing since its initial publication back in 2018, where a majority of patients with early no negative disease and recurrent score of less than 25 did not benefit from additional chemotherapy. This has now been the standard of care for these patients, but patients with higher recurrent score or options here in adjuvant settings is often TC times 4 or anthracycline based treatment. We've always wondered in clinical settings who's the right patient for anthracyclines because we have to be mindful of the side effects that come along with us. Jane, with all this in mind, thoughts on the recent updates from this study and its findings? Speaker 2 Thank you, Raghul. So I'm someone who did a lot of clinical trials and grew up in the NSABP culture where anthrocyclins are not the most favorite agents. We tried to deescalate anthrocyclins if not appropriate. I think this is a really good study. So and especially not negative patients, we tried to avoid anthrocyclins unless really indicated. So this particular study actually looked at subset of patients tailor X who had a recurrence for more than 31 or less than 31 who received an anthra cycling containing regimen versus a non anthra cycling containing regimen. So what they found was in patients with recurrence score more than 31, there is an improvement in distant recurrence free survive now. So recurrent score more than 31 and improvement in recurrency survival when they received anthocyclins and and they saw that in patients who are under the age of 50 or older than 53 minute person or post menopausal and most of the benefits were in tumor which is more than 2cm and higher the recurrent score, the benefit was higher. So that is really interesting too. The key question is are we going to use this tomorrow in our clinic? And then let's just think if I have a patient who's 52, she has a three centimeter tumor and when I it's grade 3 and it's not negative, I'm planning to give chemo, then should I use this tool to make a decision? I think I'll have a conversation with this patient about TC versus an anthracycline containing regimen or TC times 6 versus AC followed by T attack regimen. If the patient says I want everything to be done, I need to know the risk and benefit. I, I, I probably listen to that patient advocate. He said something like more information is helpful. And that's what she said. More data, more information is helpful. I may use in those subset of patient. If the patient says give me more data so that I can make the right choice, then I may use it. But if he asked me if I'm going to use for every patient, probably not. Speaker 3 This is certainly very intriguing especially this question comes about when we are treating premenopausal who are no positive but have low ONCO type score where the struggle is, is OFS plus AI beneficial or rather chemotherapy itself is beneficial now in your practice for hormone receptor positive breast cancer whose current scenario gets anthracycline and adjuvant settings? Is OFS plus AI beneficial for hormone receptor positive breast cancer? What I use is more than 4 nodes based upon the tic Tac data. We know that that's a subset of patients who benefit, you know, so more than 4 nodes, I'll say you should get anthracycline. But let's just say if the patient is younger, you know, let's just say we have a, a 32 year old with three nodes, I'll say. And for that patient, the long term risk is relapse from breast cancer rather than So then I'll say you should consider anthocycline containing regimen. But overall more than 4 knots, I'll say you should get anthocycline. Thanks for. Speaker 3 Clarifying that now moving along into our next study, which is PADMA study looking at the current role of CDK 46 inhibitor plus endocrine therapy, Is it the right approach rather which is the standard of care, But again, when compared to chemotherapy in aggressive disease, is it an appropriate approach? PADMA Study We have seen similar data with Right Choice which did establish that yes, CDK 46 inhibitor plus AI is the right approach. Jane What was the study designed for PADMA and what did it show? Speaker 2 Right. This is an interesting study. It's as you said, it's adding to the existing knowledge and strengthening our our conviction that and the treatment with CDK 4/6 is the right treatment even in first line metastatic, but if I can say high risk. So the the the study design is this about 150 patients randomized between and the treatment plus albociclib and the control arm is chemotherapy of physicians choice. These are hormones of the positive patients that go to negative indication for monochemotherapy. No prior treatment in the metastatic disease, no asymptomatic bone only or oligo metastatic. We are these are not like low risk patient the and so the patient should not have uncontrolled and or untreated CNS and life expectancy more than six months. So let's just say if I'm seeing a 42 year old a bit multiple liberation asymptomatic LFTS are normal and a lot of time I get this phone call from the in a second opinion or offering doctor say if she's young and she has multiple relations in the liver. I feel like I should be giving chemo, but I say look at the biopsy, the ERP is strongly positive or to negative. I always say let's try and treatment of course now with CDQ 46 the right choice and then this partner data reinforces our strong belief that's the right thing to do. The primary trick and point was time to treatment failure. The secondary point is progression free survival and overall survival and they had and a majority of the patients are postmenopausal and the really interesting finding is nearly 50% and nearly 50% had liver meds. The median time to treatment failure is 17 months in the Palbo and the Crone arm and six months in the control arm. Progression free survival is 18 months versus nine months. So that's a pretty significant difference between these two arms. Speaker 1 Yeah. Again, CDK 46 inhibitors with endocrine therapy is still our standard of care. This is practice reinforcing study in all comers, be it someone with visceral disease, heavy tumor burden, CDK 46 inhibitors with endocrine therapy should still be your go to. All right, Lastly, let's talk about AMBER 3. AMBER-3 James, can you walk us through this study design and findings of AMBER 3? This study got a lot of. Speaker 2 Buzz. It is published in Newman Journal at the same time, Imluna strand, it's an oral selective estrogen receptor degrader. So it's one of the third generation has CNS penetration. So this trial looked at this Imluna strand monotherapy and combined with Obama Cichlid for patients with hormone receptor positive her two negative metastatic breast cancer. They are pretreated with endocrine treatment. It's a phase three trial. It's a fairly large study. They had three arm immuno strength 400 milligram, a single agent, then standard of care endocrine treatment with fibustrin or exemestein as the second arm. The third arm is that's the one which they analyzed, that's the immuno strength 400 milligram daily plus bomber secular. And the primary endpoint is the PFS and 2nd endpoints overall survival and PFS significant improvement in progression free survival versus standard of care and the treatment in patients with ESR one mutation, the hassle ratio is .62, but it did not reach a statistical significance in overall population. So single agent newness trend is highly active. Improvement in progression free survival in tuna in patients with ESR 1 mutation and all subset of patients benefited and then an overall survey analysis are immature and it's ongoing. The safety profile profile is fairly well tolerated, no new safety signal. The second conclusion is immune strength plus Obama cycle, so significantly improved progression of his survival versus immune strength as a single agent in all patients, not just ESR one mutated all patients, the acid ratio .57 that's a pretty impressive acid ratio and and that doesn't matter if it's ESR 1 mutated and then the PFS is about 949.4 months and also the patients are benefited. So so the conclusion is enrollous strength and as a single agent in ESO unmutated patients or combined with obamaciclibin or in a patients is a potential treatment options after progression on endocrine treatment in patients are positive a her two negative and advanced breast cancer, we. Speaker 1 Do have oral cert available by itself which is LSSM, but we don't have that data as a combination. So we await for all these combination trials. The other thing I want to bring up is the control arm. We know that these patients on and the current standard of care endocrine therapy don't do well and that's the reason for us to look for these strategies of combination. But Jane, most of our patients today are exposed to abama cyclib either in first line in metastatic space or in adjuvant settings based on monarchy study. If this was to become available. Where do you see yourself using this combination? Speaker 2 So I know the metastatic ER positive spaces really I don't know what's the right term when our old patients have more options, let's just say absolutely. Speaker 1 Yes, yes. Speaker 2 When and so I think, I think that's probably the right way approaching. So let's just say I know Hal Bernstein put like a fairly complicated chart on that. So and when you see a patient you know who has an ESR 1 mutation, so now we have an option. Speaker 1 If it's available, that's. Speaker 2 In the guidelines, we have an option of using this versus the last trend. Speaker 3 Indeed, the space of oral swords is getting crowded as we already have a single agent approved in the setting, which is LSS trend as you mentioned, Rahul. And many more of these combinations are being studied as you alluded to, Jane. We'll see how it all pans out and importantly, how this changes our current landscape and future. Well, James, thank you so much for taking the time to cover some of the key studies from hormone receptor positive breast cancer space from San Antonio Breast Cancer Symposium 2024. Conclusion For our listeners, let us go or a quick recap. In today's discussion, we had a chance to focus on four key studies from hormone receptor positive breast cancer disease from San Antonio Breast Cancer Symposium 2024. This included Europa study where we are seeing that radiation was better tolerated over five years of endocrine therapy. We need long term data to select the right patients in which we can let go of endocrine therapy and radiation therapy would be rather good enough. Then we touched on Taylor X study which reported benefit with anthracycline based chemotherapy in patients with recurrent score of 31 and above. Speaker 1 We also had a chance to touch in PADMA study which continues to reinforce our current practice of endocrine therapy with CDK 46 inhibitors over chemotherapy in all comers including visceral disease and first line settings. Than before closing, we talked about AMBER 3 and the data on oral cords in combination with ebemaciclib that looks promising in all comers regardless of ESR one mutation. Thank you for joining us. Make sure to check out our other conference highlights from ASH 2024 and SAPCS 2024. We are the oncology brothers.