SECTION 1: ADCs: Datopotamab deruxtecan

Hope Rugo:

Hello, and welcome to VJOncology’s breast cancer review from the San Antonio Breast Cancer Symposium 2021, where myself, Hope Rugo from the University of California, San Francisco’s Comprehensive Cancer Center, and my colleague David Cescon are here in person on site. David, thank you for being here. Tell us where you’re from.

Dave Cescon:

Great, thank you. It’s great to be here in person with you, Hope, at the San Antonio Convention Center. I’m from Princess Margaret Cancer Centre in Toronto, in the University of Toronto, where I’m a breast medical oncologist and clinician scientist.

Hope Rugo:

Great, and now both of us had actually the tremendous honor and pleasure of discussing abstracts. I discussed abstracts yesterday morning, and you discussed abstracts this morning for two of the four plenary sessions at this year San Antonio, a little bit different organization than the past due to the virtual format of the meeting, combined format. So I think we’re gonna start discussing the first day. And you had some questions you wanted to ask.

Dave Cescon:

Yes, so you had the privilege of discussing some of the triple-negative breast cancer abstracts while I was on route down from Toronto. And those included the neoadjuvant study of pembrolizumab, KEYNOTE-522, the first-line metastatic study, KEYNOTE-355, and also the results of the phase one study of datopotamab as well in triple-negative breast cancer. Is that right?

Hope Rugo:

Yeah. I specifically discussed 522 and 355, but not datopotamab, but I’ve also been very involved in discussing those results and participating in at least one of the two planned phase three trials with that agent. But I guess I’ll talk about that first. This is a novel TROP-2 antibody linked to a toxin, which is deruxtecan, a derivative of deruxtecan, and it’s the same toxin that’s part of trastuzumab deruxtecan now approved for treating HER2-positive metastatic breast cancer. And this is a really interesting novel ADC, a little bit different from some others, and similar to, again, TROP-2 antibody, but the toxicity profile interestingly is different from sacituzumab, and so it does bring up the question of, what the variations are and the construct of ADCs that ended up creating different profiles. But this study, which was really a trial looking at four different groups, and two per inter breast cancer were hormone receptor-positive and triple-negative disease, heavily pretreated, two more lines of therapy, and single-arm trial. There was a few patients treated at a higher dose, and the majority were treated at the final dose that is moving into phase three. And this antibody-drug conjugate is given every three weeks. They saw a very nice response rate of 34%. And many of those responses were quite durable with, very similar to what we’ve seen with sacituzumab actually. About 30% of the patients appeared to have had an anti TROP-2 ADC, which since we only have one other, I assumed to be sacituzumab. The toxicity profile was also really interesting. A lot of stomatitis, grade one and two stomatitis. And apparently, this stomatitis can occur anytime during the treatment, and it really does continue as long as you’re on the drug. There’s a lot of risk mitigation strategies that are being studied. And then also they saw some nausea. But interestingly, not a lot of hematologic toxicity. So the phase three trial that’s already getting started is for hormone receptor-positive disease-

Dave Cescon:

Positive breast cancer.

Hope Rugo:

where we haven’t seen the results yet. And in triple negative disease, this study is still under discussion.

Dave Cescon:

So you’ve had a lot of, you’ve contributed a lot to the management of stomatitis for other breast cancer agents. What was your sense of the stomatitis described here as it might differ from everolimus, for example, where this has been a question in the past?

Hope Rugo:

Well, I think it actually sounds very similar. I haven’t given the drug yet, but I think with everolimus, when we were first learning about it, we really hadn’t seen much stomatitis in breast cancer prior to everolimus. So we were inexperienced with that toxicity. It’s kind of like the learning curve with ILD. And as we learned about it, we learned to stop drug if you got grade two, so you’d never get to grade three. So I assume that that learning was taking place in the treatment of patients with datopotamab or Dato-DXd. And so I’m guessing it’s probably fairly similar. There’s been a lot of interesting testing steroid mouthwash. These are just liquids, dexamethasone, or other liquid steroids to see if we could reduce the toxicity and also interest in maybe even ice. There’s interest in some of the cooling companies in sort of ice, cool, where you maybe would suck on something cold to try and reduce the delivery of the drug to the oral mucosa. Really interesting.

Dave Cescon:

Yeah, that’s interesting. I guess it wasn’t clear from the presentation how much prophylaxis against stomatitis was included in the protocol-

Hope Rugo:

There was no prophylaxis. in the study.

Dave Cescon:

No, so things may change as this agent advances into those later stage trials.

Hope Rugo:

And it will, for sure, particularly for stomatitis.

Dave Cescon:

So the evidence of some activity in TROP-2 pretreated patients is certainly very interesting. Some recent data published about acquired resistance to sacituzumab, and it looks like some of this may be antibody-related. Some of it might be cell intrinsic-related to the topoisomerase target. Here, we have another topoisomerase payload, rather, not target, but payload. So it’d be interesting to understand how these differ potentially in their activity.

Hope Rugo:

Yeah, I always tell people, remember the early nab-paclitaxel data where patients whose cancer’s progressed on paclitaxel or docetaxel responded in a reasonable number to weekly nab-paclitaxel, and this wasn’t high dose nab-paclitaxel. This wasn’t a dose issue. I think that drugs work differently, even if they’re in the same class. And we can see responses sequentially. So I wasn’t too surprised to see that. I think it’s gonna be interesting to understand where these drugs fall out. And of course, the studies that are planned for Dato-DXd are meant to try and look at an earlier line of therapy than sacituzumab, but-

Dave Cescon:

Although we expect that those studies will be coming as well, moving sacituzumbab-

Hope Rugo:

Yes, of course, with sacituzumab incentive-

Dave Cescon:

Of therapy.

Hope Rugo:

We have post-neoadjuvant studies with sacituzumab. But we do see a lot of hematologic toxicity with sacituzumab, so you need to use growth factors. So I think that it’s gonna be a balance. There’s no free lunch.

Dave Cescon:

Sure.

Hope Rugo:

But having more effective agents is really-

Dave Cescon:

Certainly in this disease. I got one other interesting note about cross-resistance or related therapies is, as I understand it, T-DXd and Dato-DXd in some of the clinical trials are not allowed in sequence, which would be another very interesting aspect of potential cross resistance or non-cross resistance for those patients who are triple-negative but have some HER2 expression, perhaps.

Hope Rugo:

So-called HER2-low. They wouldn’t even have to be triple-negative depending on the data and hormone receptor-positive disease.

Dave Cescon:

Sure, for the ER-positive that you described.

Hope Rugo:

Yeah, I think these kind of idea of sequential therapy is gonna be interesting, and it includes sacituzumab as well because hopefully we’ll see the data from the TROPiCS trial in the next year or so in hormone receptor-positive disease as well.

SECTION 2: KEYNOTE-522

Dave Cescon:

So moving on from Dato-DXd, we have the two immunotherapy studies that were presented, and these are updates of both of those trials. Which do you wanna start with? 522, start in a neoadjuvant study?

Hope Rugo:

Yeah, we can. I think the sort of combination, in a way, but so 522, as we know, was approved by the USFDA based on improvement in event-free survival at the fourth interim analysis. That was, I think, very clinically relevant. And it wasn’t just invasive disease-free survival, but also distant recurrence-free survival. So that was really encouraging. And we learned quite a number of different things. And there were some updates at this meeting, although we’re certainly looking for more. So one that we learned was that, and I’ll just start with toxicity and then efficacy. But toxicity is increased when you give the combination of a checkpoint inhibitor and chemotherapy compared to the checkpoint inhibitor alone. So there was a big drop off from the toxicity seen in the neoadjuvant to adjuvant setting. We had seen at the presentation that patients who achieved a PCR, regardless of how they got there, had a pretty good event-free survival over 90%. But patients who did not have a PCR fared significantly better if they received pembrolizumab versus the chemotherapy and placebo. We don’t know how that event-free survival was impacted by post neoadjuvant pembrolizumab at all. So there were a number of questions that came up about that, which we’ll talk about in a moment. We also learned that PD-L1 status didn’t impact any of this pathological complete response or event-free survival. We did however learn that, if you have a PD-L1 positive tumor, regardless of the treatment arm, you had a higher PCR rate, which was nice. In the PCR part, we saw that patients who had node-negative disease seem to benefit less than patients with node-positive disease. And we also saw, although there were less PCR in stage three versus stage two, the relative impact on PCR was greater for stage three than for stage two disease, which was really interesting. You look at the forest plots, and now the subset analysis presented here in the event-free survival, almost identical benefit in EFS for node-positive and node-negative, numerically a little better for node-positive than node-negative. Same with stage three and two, a little better for stage three, a little bigger elta delta, but this is really no big difference. It’s a couple of percentage points. So benefited both equally, even though clearly that PCR impact was a little bit different. And the question is, why did that happen? And that was a big part of my discussion. And I think what we have seen is that with immunotherapy that increases PCR, that you see a shift in RCB to the left. So residual cancer burden, you’re actually seeing a decrease in the amount of residual cancer burden relatively. And we know that the less cancer burden you have correlates with better outcomes. So my guess is what we’ve done is similar to I-SPY 2 data recently published by Fraser Symmans on behalf of our eyes by two group, that you really do shift that RCB curve to the left. Rita Nanda published our pembro forearm, just four doses of pembrolizumab result in a big shift in RCB downward, so to the left, using our left to right approach. And also, we saw that there was an improvement in iDFS distant recurrence-free survival and overall survival in the durvalumab study, Gepar-Nuevo, where they’ve just received development preoperatively. So really interesting data suggesting that, one, we don’t know how much I-O therapy you really need. And I don’t know if we’re gonna get to that. And two, that the benefit in PCR may underestimate event-free survival outcome. So my concern was, if you enrolled a relatively low risk group of patients like Gepar-Nuevo, you might miss a significant difference in PCR, there’s a numeric difference, but not significant, because what you’re really looking at is a shift in RCB. And there’s actually a treatment evaluation score being proposed by the I-SPY 2 group as a way to better evaluate the impact of neoadjuvant therapies, where you look at the full spectrum of RCB change, which I think will be really very interesting.

Dave Cescon:

Sure, much more to measure.

Hope Rugo:

Yes. And I showed a Twitter poll about what people would do. A lot of people answered my Twitter poll. And the question was, if you had a PCR, would you continue to complete your pembro? And about 3/4 would, interestingly, and because that’s where the data is. And the second question was, if somebody had residual disease, would you give, would you continue pembro and add either cape or olaparib, I didn’t ask that question, but everybody would add-

Dave Cescon:

Add capecitabine to the pembrolizumab, and use it in combination. So this is gonna be a challenging question for sure. With regard to that RCB, we clearly see this shift. And indeed, as you alluded to the, even in KEYNOTE-522, the overall difference in pathologic complete response to the final final analysis was relatively modest. So this RCB shift presumably reflects much of that neoadjuvant benefit. For the relationship between RCB and EFS, recognize that we’ve had that shift, do you think it still holds up if you had immunotherapy or not? Has there the same relationship between RCB-I and your prognosis, RCB-II and your prognosis? Or could the magnitude of that risk change in those RCB groups as well?

Hope Rugo:

I think it’s a really good question. And we’ll understand maybe a little bit more when we have the RCB data from KEYNOTE-522. It’s certainly an I-SPY, it appears that RCB holds up with immunotherapy, but the numbers are small. So we don’t, I don’t think we have any larger data set than that. It’s really just those two datasets.

Dave Cescon:

And certainly, in KEYNOTE-522, we spent a lot of time, our pathologists spent a lot of time globally training on RCB to be able to hopefully deliver those data to be able to conduct that analysis.

Hope Rugo:

Next year, I hope.

SECTION 3: KEYNOTE-355

Dave Cescon:

Great, so what about KEYNOTE-355? We were both involved in that study obviously, but what was your sense of the updated data that was reported at this meeting?

Hope Rugo:

Yeah, I had the honor of presenting the overall survival data because Javier Cortes who presented the data here was presenting DESTINY-Breast03 at the plenary session in ESMO. So it was kind of a fluke of too many good results, but the overall survival that is so encouraging, 6.9 months. And I think that that’s great. It sort of solidifies the role of pembrolizumab in chemo, gives us a menu of chemo or shorter disease-free interval. And basically, a lot of questions came up after that presentation and approval, of course, with proved early and late stage in the US, which was, does it matter if there’s incremental differences in the combined positive score, CPS? So if they did less, 10% or more, and 1% or more. What about one to nine? So this presented that whole spectrum, one to nine, 10, over 10, over 20. And it turns out over 10 is still the best cutoff, so that’s basically what the presentation showed. I think it brings up a question about the particular test you do, which of course, in this situation, we use CPS with the 22C3 antibody. I mentioned that we still really don’t know why I’m IMpassion131 was a negative trial with paclitaxel, and we need to look at the heterogeneity of the tumors in that study to understand, because the overall, it’s not just that atezo didn’t work, it’s that the control population did like, I don’t know, 10 months better than we would expect in a control population. So I wonder if they had a more luminal-like triple-negative disease, disease that was ER-positive or apocrine-like, or any number of different subsets, adenoid cystic that are, that tend to be more therapy-

Dave Cescon:

Behave differently.

Hope Rugo:

Responsive and indolent, and patients live longer. And then the last question was IMpassion130, tocilizumab is still approved in many parts of the world, just not in the US, and it is-

Dave Cescon:

Including in Canada, yeah. Although access is limited because the Abraxane is not readily available in Canada.

Hope Rugo:

I see. Yeah, that’s interesting, a nab-paclitaxel shortage in the US right now, So the question was, is that really a negative trial? And I think the answer in my mind is sort of a statistical. This statistical plan led to an unfortunate result, which doesn’t actually mean that atezo doesn’t work, but there are too many unanswered questions. It’s interesting that the delta was seven months at the same timeframe at 6.9 months for pembro. And so there’s clearly a survival benefit. It’s just that we just do not understand the kind of oddities of why 131 wasn’t positive. And then the statistical design of 130, which required that they have confirmatory data.

Dave Cescon:

And indeed, the statistical design of many of these immunotherapy studies have been critical to their success or failure. And KEYNOTE-355, when it was initially designed, didn’t have the 10% cutoff, it was based on 1%. So those changes were done before the data was available. But clearly that has identified a threshold, which has been essential for the success of KEYNOTE-355.

Hope Rugo:

Yeah, they were lucky.

Dave Cescon:

Yeah, we saw some, I think some recent data this week as well, looking at TMB, for example, with immunotherapy, and similar findings that refinement of those thresholds can make a big difference.

Hope Rugo:

Yeah, I thought the TMB data from today was quite interesting. And the NIMBUS trial was a combination of two immunotherapies, ipilimumab and nivolumab, and a low dose of ipilimumab, because the combination at a high dose has really resulted in a ton of toxicity, a lot of adrenal insufficiency as well. Although some durable responses, it’s really not workable. That study was interesting to me because I think they did a nice job, but it doesn’t tell me anything to move ahead with yet. I think that in high tumor mutational burden, checkpoint inhibitors are effective. Whether or not you need to give doublet therapy, we don’t know. And that’s, I think, the question that arises out of that particular study.

Dave Cescon:

Sure, and really any single arm immunotherapy study in breast cancer now is complicated by the fact that the patients who are selected to be enrolled in those trials are selected for many reasons, right? Not only the TMB, but there are other things that can’t be well quantified in the study report by their physicians and the enrolling investigators.

Hope Rugo:

But PD-L1 didn’t make a difference, which-

Dave Cescon:

In the study, that’s interesting.

Hope Rugo:

TMB can way over the patients I’ve had who’ve had very long duration responses to a single agent checkpoint inhibitor with pembrolizumab had, and these are lobular cancer patients who have just terribly resistant, awful disease. They all had tumor mutational burdens of like 60. So it does, I think, I had already sort of decided that must predict who benefits. So it was nice to see that as well. And those were people who did have very high numbers, but tiny, tiny numbers.

Dave Cescon:

So I have, I’m fortunate to have a number of patients who have had very prolonged and durable benefit of pembrolizumab with triple-negative breast cancer, who participated, well, some of them got pembrolizumab, others were treated on clinical trials, and I don’t know if they got pembrolizumab. But seeing that, you mentioned the delta and the progression in the median overall survival of these curves. We know also that there seemed to be plateaus in these curves with the longer followup in KEYNOTE-355, including in overall survival. And there, again, PD-L1 seems to make a difference. The 10% to 20% cutoff, we see a larger number of patients achieving that triple benefit. One question that I’ve had, and we’ve seen the KEYNOTE-119 data where patients with higher PD-L1 levels treated with pembrolizumab monotherapy could have responses. So for these patients with high PD-L1 levels, and indeed in 355, we see some patients who have quite high levels, do they really need the chemotherapy? Could some of these people, could some of these patients achieve long and durable benefit and avoid the toxicity of chemotherapy that comes with that upfront combination?

Hope Rugo:

It’s a great comment and thought, I think, even in the group, small group in KEYNOTE-119 that looked at single agent pembro in the second and third line, there were better survival, but it wasn’t like stunning. So I think-

Dave Cescon:

It’s about one in seven, about one in seven participants had a response. So it’s clearly, or one in seven participants had PDO, one of 20% of them, 20 or 30%, I think, achieved a response.

Hope Rugo:

Yeah, and then the responding patients did well. They had longer survival on a subset of a subset, but I don’t know how that really translates into how we should treat people in clinical practice, ’cause they’d still get chemo.

Dave Cescon:

Absolutely.

Hope Rugo:

I do have long-term survival with checkpoint inhibitor therapy alone, as you mentioned also. I stopped at five years because she kept having colitis.

Dave Cescon:

So this was with continued checkpoint therapy for five years.

Hope Rugo:

Yeah. She was on the original KEYNOTE-086 trial.

Dave Cescon:

Was that the two year-

Hope Rugo:

In the second and greater line setting where the response rate was 6% in PD-L1-positive disease. She had a CR in lung. And I think probably some of it depends on where your disease is, and then just some luck that we don’t understand yet. Giampaolo Bianchini, who presented some interesting data on spatial analysis on the first morning, that I won’t review because it’s complicated, but it’s really interesting actually how close the cells are together and everything. But he also has this IO score that he’s been working on for the NeoTRIP trial. So we’re all, I think everybody’s working on ways of looking at combined analyses to try and figure out if we can understand who benefits, who doesn’t need checkpoint inhibitors, et cetera. But I’d love to move on to some of the talks that were today.

SECTION 4: EMERALD

Hope Rugo:

And I think the talk that had the most sort of press and discussion and will continue to was the EMERALD trial, testing elacestrant. Tell us, you discussed that. Tell us all about-

Dave Cescon:

Sure, so EMERALD, this was the, Dr. Bardia presented the first phase three trial of one of the novel oral SERDs in breast cancer. And this study randomized participants who had had one or two prior lines of endocrine therapy for metastatic breast cancer to elacestrant, or a standard of care endocrine therapy. And here, the standard of care was physician’s choice, which could include one of three aromatase inhibitor or fulvestrant. So a pragmatic study, which meant that there’s a mix of patients who have had one or two prior lines with second or third line endocrine treatment, and about 20% of patients had also had one line of chemotherapy. So perhaps a little bit different than what we might see today, or if we were planning a study today where most people get AI, get a CDK4/6 inhibitor in the first line, and much of our focus is really on understanding really the more pure second line population, I think. But clearly exciting to see these data for a new agent and a new class of agents. This study, interestingly, was designed with two primary end points, progression-free survival and the overall intent to treat population, and progression-free survival in the ESR1 mutant population. You know that ESR1 mutations are obviously important for acquired resistance to endocrine therapy, particularly aromatase inhibitors. And roughly 40% of the population of the trial had an ESR1 mutation, has detected in everyone by a circulating tumor DNA assay at the time of enrollment. So both of those primary end points were positive. The magnitude of benefit was larger. The hazard ratio was smaller. The magnitude of benefit was larger in the ESR1 mutant population. Here, sort of like the KEYNOTE-355 data, we don’t have the data for the ESR1 wild type patients. We only have the intent to treat and the mutant population. So it’s sort of like that one to 9% population, what happens in them. Mathematically, it looks like there’s probably not a large benefit in the ESR1 wild type population, and there wasn’t a forest plot included for that, but we’ll look forward to see how that group may or may not benefit from this agent. Importantly, what we’ve seen in the setting, and we’ve seen in prior studies of post CDK4/6 inhibitor treatment is that many patients unfortunately do very poorly with endocrine monotherapy. This was seen in Veronica as presented at ASCO this summer, study of fulvestrant with or without venetoclax in their progression-free survival with fulvestrant monotherapy of about two months. And same thing was seen here with the treatment of physician’s choice, the standard of care arm progression-free survival was shorter than the first interval scan. So I think this clearly emphasizes the need to improve our treatments for the CDK4/6 resistant setting overall. But beyond that initial drop-off, there seems to be a separation of those two curves maintained with elacestrant. And importantly, this is a drug which seems to be pretty well tolerated on the basis of the recorded treatment-related adverse events, GI toxicities, including nausea, vomiting, were the principal toxicities that were increased. I think for these, the patient reported outcomes will be very important to understanding the quality of life on this agent, as opposed to fulvestrant, for example. So much excitement in the development of oral SERDs. This is a large class of agents, more than 10 agents currently in clinical trials, including about five that are in phase three trials, really ranging from the adjuvant setting all the way through to metastatic combinations with targeted therapy. So we have a lot to learn. I think we’ll learn a lot more from the EMERALD data. As those correlative analyses are performed, we really begin to understand who is that group of patients, both molecularly and clinically, who progress quickly on second or third line monotherapy and require something else.

Hope Rugo:

I’m gonna ask you a question. So there were a few thoughts that I had in just hearing this data that, and they’re, I think they still sort of worry me a little bit that patients first proportion had prior fulvestrant. Those patients had to go on an AI. They were quite likely to find an ESR1 mutation. So it was not too hard to beat an AI in a patient with ESR1 mutation. We didn’t see that breakdown. So that’s one thing. The second thing is the deltas were really small, even though it was highly statistically significant. The hazard ratios were good. The delta for the entire population was less than a month in terms of PFS. And for the ESR1 population was less than two months, almost two months. And then, so the third question, just so I get them all in there is that, yes, it’s oral and really well tolerated compared to what we saw in previous generations of oral SERDs. But thinking about getting an injection once a month, particularly if you’re Medicare, it’s completely covered, you’re gonna take a really expensive pill. And maybe, I was looking at the vomiting, it was all low grade, grade one-ish, one, grade two.

Dave Cescon:

Maybe important for-

Hope Rugo:

It was 20%, so I don’t know what that means. If you feel nauseated half of the time and it’s low grade, is that, and you’re spending more money, is that better? I don’t know. And they talked a lot about the six and 12 month PFS. And the question is, why do we see that if we don’t see the longer, bigger separation?

Dave Cescon:

So the question about the prior endocrine therapy is of course very important for the study, where in a pragmatic second, third line study, patients were allowed standard of care mixed agents. And based on the 50% of patients having had one line of metastatic therapy, the other 50% or so having had two lines, plus roughly two thirds of patients having had adjuvant endocrine therapy, we can expect that all participants would have been exposed to an aromatase inhibitor. And certainly the ESR1 mutations are likely arising in the context of prior AI therapy. But 145 of the 570 or so patients had had fulvestrant. And so those patients who had had prior fulvestrant are likely being retreated with an AI in the standard of care arm here. Dr. Bardia did show in his presentation the comparison of elacestrant versus fulvestrant for the patients who had fulvestrant. So I think this was helpful to contextualize the results in what would not represent re-treatment with an agent that had already been exposed to. I understand that there was a small number of patients who had had fulvestrant, who were retreated with fulvestrant, but we’ll need to see those data, I think, in forthcoming presentations.

Hope Rugo:

Yeah, it’s interesting. So just as we finish up with this really interesting discussion, would you prescribe this drug? Which we’re all pronouncing a little bit differently, but I like your presentation. Is this enough benefit to merit the cost of an oral drug?

Dave Cescon:

Well, so this question came up in the discussion as well. Does it merit the cost? We don’t know what the cost of this drug is.

Hope Rugo:

It would be more than generic fulvestrant.

Dave Cescon:

It would be more than, it will likely be more than generic fulvestrant, but this is a new endocrine therapy. We haven’t had a new endocrine therapy in breast cancer in a long time. So will this be-

Hope Rugo:

A few decades.

Dave Cescon:

Will this priced like the latest oral-targeted therapy? Or will it be priced in a different way? And I think that value for therapy is critically important, certainly in Canada and increasingly in the US and around the world. And understanding those costs and the benefits that are associated with them is critically important, especially where, as Dr. Bardia described, many of these agents will be developed in combination with other expensive targeted therapies. So would I prescribe this agent? Again, I think we need to see a lot more data. I would like to be able to understand the patient-related quality of life. Fulvestrant is a very well tolerated drug, apart from the injection that’s administered twice a month. So I think this supports that this is a class of therapies that can have impact, that may be tolerable, and how this fits in our bigger context of treatment of ER-positive breast cancer. And how it fits into the economic context of our treatment of cancer in general remains to be seen.

Hope Rugo:

Yeah, it is interesting. I was thinking about patients in the second line setting, they could still stay on an oral drug if they tolerate it well. They have a longer PFS at six and 12 months compared to other therapies. If you really understood the nitty gritties of the fulvestrant, et cetera, use, and they have an ESR1 mutation, potentially, that could be a big quality of life improvement, all cost aside, if they didn’t have toxicity. But it’s fascinating, and I think we’re looking for a lot of more data on the oral SERDs in the next year and two. Many trials going on, and of course, elacestrant will also, I think, move to earlier trials and new development as well. With that, I think we’ll conclude our discussion of these really interesting topics from the San Antonio Breast Cancer Symposium in 2021. Thank you for being here with us in San Antonio, Texas, and to VJOncology.

Dave Cescon

Dr Cescon reports the following conflicts of interest:
Consulting/Advisory Boards: AstraZeneca, Dynamo Therapeutics, Eisai, Exact Sciences, Gilead, GlaxoSmithKline, Merck, Novartis, Pfizer and Roche.
Research funding to institution: GlaxoSmithKline, Inivata, Merck, Pfizer, and Roche.

Dr Cescon additionally reports a patent (US62/675,228) for methods of treating cancers characterized by a high expression level of spindle and kinetochore associated complex subunit 3 (ska3) gene.

Hope Rugo

No disclosures provided