Breaking News: Updates from the 2024 ASCO Annual Meeting

LBBC welcomes medical advisory board member Rita Nanda, MD to share the most recent breast cancer findings from the 2024 ASCO Annual Meeting. Learn the latest medical breast cancer research presented at this year’s ASCO Annual Meeting and how this news may impact you. Attendees had the opportunity to ask Dr. Nanda questions during this free webinar. 

Transcript

Rita Nanda, MD [00:00]

Hi, good afternoon.

Thank you so much to Living Beyond Breast Cancer for having me here today. It’s my pleasure to be here. I hope the slides, everyone can see them OK. And I just wanted to highlight some of the interesting studies out of ASCO this year. By no means is this comprehensive. I also wanted to just show you my disclosures as well.

This is by no means a comprehensive update, but I just wanted to pick a handful of studies that I thought will possibly be impacting how we practice medicine, and it may impact some of the care that you receive in the clinic. Then some promising regimens that are in development that may be coming in the not too distant future. But again, you know, in the interest of time and also having time for question and answer, I just picked five studies that I thought met that bar.

I’m also going to be talking a little bit about some of the other studies that were presented there. So I’m going to start with three studies that I think are ready to change practice now. Potentially these are regimens that I think your physicians in the clinic may be aware of and then some newer studies that may be coming down the line.

One of the late-breaking abstracts that was presented this year was a clinical trial called DESTINY-Breast06. This is a trial that investigated a drug that’s already being used out there in the clinic, trastuzumab deruxtecan, I think many of you probably refer to it as Enhertu. This treatment has been approved for a number of years for HER2-positive breast cancer, and then a couple of years ago at ASCO we saw a trial which led to the approval of trastuzumab deruxtecan for HER2-low breast cancer.

The trial that was presented at ASCO this year was looking at the same drug, Enhertu, versus chemotherapy of physician’s choice in women with hormone receptor-positive metastatic breast cancer, so ER- and/or PR-positive metastatic breast cancer. And in this trial they looked not only at HER2-low, but this new sort of definition of HER2 expression called HER2-ultralow.

I think everybody knows that there is a subset of patients who have HER2-positive breast cancer. And we figure this out by doing staining on tumors using immunohistochemistry. And we look at breast cancer tumors and how high of an expression level they have of the HER2 protein. If the HER2 is high, like a 3+. So the scale is zero, 1+, 2+, 3+.

If it’s 3+, that’s considered HER2-positive. And if you have HER2-positive metastatic breast cancer, you’re eligible for treatment with Enhertu, and have been for a number of years. HER2-low is 1+, 2+, and that was the approval for Enhertu came a few years ago for that population of patients with metastatic breast cancer.

But in this study the question was, well if you have a little bit of HER2 expression, but it doesn’t meet that definition of HER2-low, can you also benefit from Enhertu? And so that’s what this study was designed to look at in women with metastatic hormone receptor-positive breast cancer. And so in this study, patients who were eligible who had either HER2-low or HER2-ultralow were randomly assigned to Enhertu or chemotherapy, a physician’s choice. And that could be capecitabine, nab-paclitaxel, or paclitaxel, also known as Xeloda, Abraxane and Taxol.

What we found in this study was that trastuzumab deruxtecan was better than traditional chemotherapy. It helped patients’ cancer remain under control, something called progression-free survival for on average 5 months longer. So those patients who got Enhertu had their cancer remain under control for 5 months longer than traditional chemotherapy. And that was really exciting to see.

Rita Nanda, MD [04:44]

We’d already seen this in HER2-positive and HER2-low disease. But now including that group of patients with just really barely any HER2 expression, we also saw that same benefit. And so I think that this is going to very likely change practice in the not too distant future. I think for my patients who have HER2-ultralow breast cancer, based on these data here—this was looking specifically at those patients who had HER2-ultralow, you can see that there was the same almost 5-month benefit in the cancer remaining under control for longer with Enhertu versus chemo—that I’ve already started incorporating this into my practice in the clinic.

And that’s because this drug is already commercially available. Sometimes it just requires us to, you know, file an approval with the insurance company to get it for patients who fall into this category. But it’s really exciting to see these results, and I very much think in the future, and there’s a trial ongoing looking at HER2-negative patients, so no expression at all in that patient population. That trial is already ongoing and it very well may expand the approval to it doesn’t matter what your HER2 expression level is, if it’s zero to 3+, everybody can benefit from this drug. I think that’s where we’re heading with this drug for this for patients with metastatic breast cancer.

The other thing I want to mention is trials looking at Enhertu in early-stage breast cancer are already ongoing, whether you’re HER2-positive or HER2-negative, those trials are already ongoing and showing early success.

So while right now this drug is approved for metastatic disease, I do think that we’re going to take the improvements that we’re seeing here in the metastatic setting and very likely improve outcomes for women with early-stage disease. Now that’s still a number of years away, but I just wanted to let you know that trials are already ongoing looking at moving this drug up into the early stage setting. So very exciting to think about what the future is going to hold for this drug.

There are obviously side effects, there are side effects with any therapies that we give, but when we’re looking at the number of patients who can benefit from this drug versus chemotherapy, again, you know, looking at those with HER2-low disease, you know, response rates are kind of in the 60% range across the board, whether you’re HER2-low or HER2-ultralow. And that’s about double what we see with traditional chemotherapy. And so that’s really the excitement of Enhertu and actually all of the drugs of this class.

Enhertu is what I like to refer to as targeted chemotherapy. It’s chemo but there’s an antibody that helps shuttle the chemotherapy to the cancer cells. So it’s more effective because we are really helping to get that chemo to the tumor and the tumor cells a little bit better than just with chemotherapy alone. So I think we’re seeing an explosion of drugs of this class, these antibody-drug conjugates.

Some of these targeted chemotherapies are targeting different things on cancer cells and then obviously all different kinds of chemotherapy that get gets delivered to the tumor. So you know, different kinds of side effects we’ll see with these different agents, but I think a lot of excitement about this class of drugs called antibody-drug conjugates or targeted therapies, targeted chemotherapies. And I do think that eventually we’re going to be using these drugs more than we are the traditional chemotherapy drugs that we’re using now.

Jean Sachs, MSS, MLSP [08:55]

Dr. Nanda, let me just jump in and ask two questions while you’re on Enhertu. And it is exciting to see the success and also expanding.

One question is about has there been any pushback for insurance covering this drug. And then also—and you may not have these studies yet—but are they seeing a difference in responsiveness if you’re ultralow versus low or high in its effectiveness?

Rita Nanda, MD [09:24]

Yeah, really great questions.

In terms of insurance approvals, well these data are new. For HER2-positive and HER2-low breast cancer, this drug is already approved and already out there and is covered by insurance companies generally. Sometimes we have to do prior authorizations and things like that, but generally thye’re covered.

Now this HER2-ultralow, this is hot-off-the-press data, but I will say that I do think with these data and how impressive they are that we can appeal to insurance companies to get the drug approved there. I’ve been successful also at, in the past, getting compassionate use from the drug company that manufactures this drug for those patients who were ultralow or zeros before. And so I have used it in those situations and have been able to get it either through insurance approval or through compassionate use from the company.

So I do think that it’s possible to get this, sometimes it requires a little bit of extra work for the doctors, but obviously we’re here to serve our patients and try to get them all of the therapies that they can have that can benefit them.

In terms of the data that you’re referring to, ultralow versus low. So I’ve shown you data for ultralow here. That’s what was presented at ASCO this year. We are seeing, and this is specifically for ultralow patients, we’re seeing the same benefit with ultralow that we’re seeing with low.

With HER2-positive breast cancer, which is where the first approval came, the benefits are even greater. So it does seem, whether you’re HER2-positive or HER2-low, ultralow, there is a little bit of a difference in terms of responsiveness and effectiveness, but still this drug is better than traditional chemotherapy for patients regardless of the expression levels.

And I do think we’re going to get to the point down the road, now this may be a number of years from now, where we probably won’t even bother checking HER2 status and all patients with metastatic disease will be able to have access to this drug.

Now, I don’t know, I could be wrong. There’s a trial ongoing now, we don’t have the data for the HER2-zeros, but there was a trial that was done in Europe a few years ago looking at HER2-zeros. It was a small study and it showed benefit there too, about a third of patients who had HER2-zero expression seemed to benefit as well. And it’s really on the basis of that trial, the DAISY trial, that I’ve been able to get insurance companies to cover it even prior to this presentation at ASCO for my HER2 zeros, or I’ve been able to appeal to the pharmaceutical company for compassionate use.

And so I think that’s where we’re heading with this drug, which will obviously make it much easier, because our pathologists look at us like, “Why do you care about HER2-low and now ultralow and all of this?” [When we’re] going back to pathology and having them re-look at slides. We do it all the time, but it would obviously be much easier if we don’t have to do that.

I hope that addressed the questions that were asked, but please keep putting your questions in the chat. I’m happy to take them in real time. So let’s do that and hopefully we’ll have a little bit of time at the end for any other questions.

Jean Sachs, MSS, MLSP [12:59]

I’ll ask one. I’ll ask one more question.

Rita Nanda, MD [13:02]

Yeah, sure.

Jean Sachs, MSS, MLSP [13:03]

Some of the people on the call who have triple-negative metastatic breast cancer, they’re wondering if Enhertu would ever be an option for them.

Rita Nanda, MD [13:12]

Yes, it is. Right now the approval for Enhertu is for HER2-low, and about a third of patients who have triple-negative breast cancer have low HER2 expression. So this drug is already approved before ASCO this year for that subset of women with HER2-low, triple-negative breast cancer.

Now this study with the ultralow was done in hormone receptor-positive disease, but I think many of us will probably extrapolate these findings to triple-negative disease and use the drug in that setting as well. Again, it will, you know, it’s not the actual approval but I think a lot of times we’re able to negotiate with insurance companies and also try to get compassionate use for patients. So I do use this drug for my HER2-low patients with triple-negative breast cancer. Great question, and I’m sorry I didn’t cover that. That’s data from a few years ago, so it’s already out there and being used for this indication.

Another question or?

Jean Sachs, MSS, MLSP [14:28]

No, I think you can keep going, but thank you.

Rita Nanda, MD [14:31]

All right. So now to move on, I wanted to talk about this study called the postMONARCH study. And this study was looking at patients who have hormone receptor-positive metastatic disease who’ve gotten a CDK 4/6 inhibitor. So that’s palbociclib, ribociclib or abemaciclib in the frontline setting and then have progressed. And this study looked at continuing a CDK 4/6 inhibitor abemaciclib in the second line setting.

For women who have estrogen receptor-positive breast cancer, we always like to use anti-estrogen based therapies in that frontline metastatic setting if we can. And we always use a CDK 4/6 inhibitor. So palbo, ribo, abema, also known as Ibrance, Kisqali and Verzenio, for all of you out there who may have been on these drugs.

When that first-line treatment stops working we move on to something else. Well, there’ve been studies out there that have shown maybe continuing the CDK 4/6 inhibitor with a different anti-estrogen therapy may be of benefit. Some studies were negative, some studies were positive.

This was a large, randomized phase III study that looked at using abemaciclib or Verzenio in that second-line setting after people have stopped responding to their first line therapy, was there benefit to continuing that targeted therapy, that CDK 4/6 inhibitor.

In this study patients were randomized to fulvestrant — which is another name for Faslodex, which is an anti-estrogen therapy that’s given by injection once a month — or adding a CDK 4/6 inhibitor, continuing it in that second-line setting with the Faslodex. And what we saw in this study was that continuing a CDK 4/6 inhibitor, in this case whether patients got Ibrance, Verzenio, or Kisqali, doesn’t matter. But then when they went on to get the Faslodex in that second-line setting, they were given either a placebo or they were given Verzenio. It showed that continuing CDK 4/6 inhibitor-based therapy, so giving Verzenio with the anti-estrogen therapy, was better than giving the anti-estrogen therapy alone.

It was modest, so it wasn’t like doubling the amount of time the cancer remained under control, but it did add a benefit with really not much in the way of side effects. And when you look at patients 6 months after they started this regimen, well, 50% of the patients who were on the combination of Verzenio and Faslodex were still on therapy versus about a third of patients who were on the Faslodex alone. So I do think this is going to change practice.

Now I’ve seen patients who, you know, their physicians have continued on a CDK 4/6 inhibitor in the second-line setting, but we finally have some data that suggests it’s a good strategy.

We have a lot of other types of therapies that people can benefit from with Faslodex. If patients have a PI3-kinase [PI3K] pathway alteration. There are drugs like alpelisib [Piqray] and capivasertib [Truqap] that are approved to be given with fulvestrant. If women have an ESR1, an estrogen receptor mutation, there’s a drug called elacestrant [Orserdu] that is approved. But for about half of women they don’t have those mutations. Now we have another strategy that can help the cancer remain under control longer giving Verzenio with the Faslodex in this second-line setting.

It’s nice to have an option for those patients who aren’t candidates for some of these other drugs.

Piqray is another name for alpelisib, I’m sorry I don’t remember the name for capivasertib. And elacestrant is Orserdu.

Not everybody’s a candidate for those therapies. And now, for those who aren’t, we’ve got another strategy here. So this I think will definitely change practice right away.

Verzenio is already approved, it’s already out there. So when drugs are already approved and available, we as physicians can incorporate them into clinical practice right away. That’s the case for the Enhertu that I just talked about and for the Verzenio here as well. I think exciting to think about another targeted therapy option for patients with hormone receptor-positive metastatic breast cancer. I’m happy to pause there if there are any questions or I can keep moving along.

Jean Sachs, MSS, MLSP [19:28]

Yeah, I think you can keep moving, that would be great.

Rita Nanda, MD [19:31]

OK, so then I wanted to talk about a study called PATRICIA. This was a study that looked at targeted therapies, the same type of drug, the CDK 4/6 inhibitor palbociclib, or Ibrance, in patients with HER2-positive breast cancer.

In patients with HER2-positive breast cancer, we’ve got the Enhertu, which we’ve already talked about, but proportionally, about half of patients with HER2-positive breast cancer are triple-positive. So they’re not only HER2-positive, but they’re also estrogen receptor-positive. And for these patients we’ve primarily focused on giving them chemotherapy with Herceptin, Perjeta, and therapies like that.

But this trial was looking at those patients who are both hormone receptor-positive and HER2-positive and looking at those therapies that we use for patients who have hormone receptor-positive disease, right? Anti-estrogen therapy, these CDK 4/6 inhibitors, and comparing that plus Herceptin with chemotherapy plus Herceptin to say, is there a possibility that we can get some really nice responses before we need to move to chemotherapy for these patients.

This trial looked at Ibrance, Herceptin, anti-estrogen therapy versus chemotherapy and it was chemotherapy, a physician’s choice, it could be vinorelbine, capecitabine, eribulin, paclitaxel, docetaxel, so a chemotherapy with Herceptin. What this study found was that giving the more targeted therapy approach, anti-estrogen therapy, the CDK 4/6 inhibitor Ibrance and Herceptin was actually better than chemotherapy plus Herceptin. It’s really nice to have this data for patients who are triple-positive, or hormone receptor-positive and HER2-positive, because it gives us another option maybe before we even need to move to chemotherapy in these patients.

Ibrance, the anti-estrogen therapy, are generally pills. Patients can take those at home by themselves and then just come in for a Herceptin infusion or even get the injection form of Herceptin potentially. So again, exciting to see that we’re refining our ability to treat patients and we’re giving more personalized therapy and that those personalized therapies can benefit patients. For those patients who are hormone receptor-positive and HER2-positive, we’ve got a newer strategy that we can use potentially instead of chemotherapy for these patients. So that was really exciting to see. And again, these drugs are all available, we can kind of roll this out into clinical practice sooner rather than later.

Jean Sachs, MSS, MLSP [22:31]

I’m going to ask one question, two questions actually, going back to Verzenio if that’s OK.

One question is with this: With combining it with fulvestrant, are you taking the same dose of Verzenio and for those that are going to add fulvestrant, if they weren’t on Verzenio first?

Are they doing better if they switch? I think that’s what that other question is.

Rita Nanda, MD [23:02]

I’m sorry, the first question here, this Ibrance dose. I’m sorry, are you...

Jean Sachs, MSS, MLSP [23:10]

I was going back to your earlier, the...

Rita Nanda, MD [23:14]

You want to go back to the first? This one?

Jean Sachs, MSS, MLSP [23:17]

The slide about adding fulvestrant with Verzenio.

Rita Nanda, MD [23:23]

OK. The postMONARCH study.

Jean Sachs, MSS, MLSP [23:25]

Yeah.

Rita Nanda, MD [23:26]

And, and I’m sorry, you’re asking about the dosing?

Jean Sachs, MSS, MLSP [23:29]

Yeah. Is the dose of Verzenio the same as when patients were taking it without fulvestrant?

Rita Nanda, MD [23:37]

No. Verzenio has been approved for a number of years, all by itself for patients who’ve never had this class of drug before. And the dose there is 200 milligrams, twice a day. When all of the studies — this study and the other studies — looked at Verzenio with anti-estrogen therapy, the dose is lower, it’s 150 milligrams, twice a day.

Jean Sachs, MSS, MLSP [24:02]

OK, that was the question. Thank you.

Rita Nanda, MD [24:05]

Yeah. And that is on the label, all the doctors out there should know that. When it’s given by itself the dose is different. But we really don’t give it by itself anymore because that study that was done that led to that approval for Verzenio to be given by itself was before we had the approval for Ibrance, Kisqali, and Verzenio in the frontline setting. So that’s not typically given by itself.

But yes, absolutely, it’s a great question. When we give it in combination, it’s a lower dose. And sometimes we have to reduce the dose because people are having side effects and that’s OK. There have been studies that have shown even when you have to reduce the dose of Ibrance, Kisqali, Verzenio, that patients do equally as well. So you should not be alarmed or concerned if your doctor wants to reduce the dose to make it more tolerable for you because I think that’s a really important thing that we need to do to make you know your quality of life better.

And I’m sorry, the other question, I missed it.

Jean Sachs, MSS, MLSP [25:11]

No, you should keep going. We have a lot more to cover.

Rita Nanda, MD [25:14]

Yeah. OK. So I think the PATRICIA study to me the really exciting thing here is that anti-estrogen therapy, a CDK 4/6 inhibitor and Herceptin, are better than chemo and Herceptin for patients who have hormone receptor- positive, HER2-positive disease.

And I think this is something that we can start incorporating into our practices right away and just really exciting to think about. Response rates were higher when we used the targeted approach versus chemotherapy, about one in five patients responded as compared to just 7% and the cancer could remain under control for quite some time. So definitely something that is exciting to think about.

And for those of you who have triple-positive metastatic disease, it might be something you want to talk to your [doctors] about at some point whenever you and your doctor think it’s appropriate.

And again, these drugs are all out there, available, and it may require a negotiation with the insurance company until the approvals come through, but definitely something that can be considered.

Now I wanted to shift gears and talk a little bit about things that maybe aren’t in the clinic yet but may be coming down the line.

This was a study that was first presented at San Antonio and then we saw an update at ASCO this year. So exciting data. This was a study, there is a drug called alpelisib or Piqray, which is already approved for women who have hormone receptor-positive metastatic breast cancer and have a mutation in the PIK3CA gene. And that’s about a third of women with hormone receptor-positive metastatic disease who have that mutation.

Alpelisib is already out there and approved. We generally start with, as you’ve seen, CDK 4/6 inhibitors and anti-estrogen therapy in the frontline setting. And then move for those one third of women who have this mutation in their tumor to drugs like Piqray or capivasertib in the second line setting with fulvestrant. But this trial looked at three drugs in that frontline setting to see if three drugs are better than two.

For those patients who have mutations in the PI3K gene in their tumor, and like I said about a third of women with metastatic hormone receptor-positive breast cancer do. It looked at adding a cousin drug to Piqray called inavolisib with Ibrance with fulvestrant.

Three drugs targeting PI3K, targeting CDK 4/6, and the estrogen receptor versus just the CDK 4/6 inhibitor and fulvestrant alone. And there was a placebo for the inavolisib here. So it’s looking at does the triplet combination do better than just two drugs, the doublet.

What was found here is that yes, if you add a PI3K-inhibitor — a drug like Piqray but not Piqray, a cousin drug made by a different company — that the cancer remains under control longer, significantly, as compared to just giving the Ibrance and the Faslodex alone.

And so this was really exciting. It kept the cancer under control for about twice as long. So 7 months for the two-drug regimen versus 15 months, so over a year, for patients with the three-drug regimen.

Now inavolisib is not yet FDA [Food and Drug Administration] approved, but I suspect that it will be based on the results of this trial. So we may be looking down the road where, when patients are first diagnosed with metastatic breast cancer and for those third of patients who have a mutation in the PI3K gene that we may be looking to give three drugs instead of two.

Now I will say adding that third drug does add side effects. The PI3K inhibitors as a group have some side effects that that can impact quality of life. It can cause the blood sugars to go very high, so hyperglycemia, it can have diarrhea, a rash, irritation of the mouth — so sores in the mouth.

For the most part, these are lower grade and manageable side effects. They usually happen early and if you can get them under control then patients can continue on with the treatment. But this may not be a strategy for everyone. Number one, it’s only for those third of women who have mutations in this PI3 kinase gene. But for some patients it may be an option and they may be able to tolerate it. So I think this is a combination that may be entering the clinic in the not too distant future, and I just wanted to make you all aware of it.

I think if this regimen were approved, for my patients who are on Faslodex and Ibrance and doing just fine, I might not rock that boat. But it’s interesting to think about some of those patients who may have really aggressive disease and we really need to get it under control quickly. This may be something that I would consider doing on a case-by-case basis for some of those patients as they’re newly diagnosed with metastatic disease. So I just wanted to put this out there.

Everything we do comes with the potential for side effects and in the metastatic setting we really need to balance the effectiveness of a regimen with the side effects. I put this up here just to show you that for the high blood sugars, the diarrhea, the rash, the mouth sores. In the sort of blue lines, here are the patients who develop these side effects who were on the three-drug regimen. And you can see, and this is over time, for the most part, people develop these side effects early and if you can get it under control then they can stay on this treatment and have it be pretty well controlled.

The rash too, although sometimes it sneaks in later on, this is you know, 3 years after. But for the most part, within the first few months here you can see the high blood sugars, the rash, the mouth sores, and then you know it really drops off after that. You’re not seeing too many blue bars later on or at least to the same level. So we really can figure out how to manage the side effects over time.

Jean Sachs, MSS, MLSP [32:20]

Dr. Nanda, I just want to ask one question, well really two.

One of our listeners who does have metastatic breast cancer is wondering if you use a multi-drug as in the first line setting, does that remove some of your options? Because obviously anyone living with metastatic wants to keep their options open. So if you could address that.

Then just a general question, and I think we talked about this, but more happened at ASCO for the hormone-positive than triple-negative. But if there’s anything you want to share about triple-negative, I think that would be appreciated.

Rita Nanda, MD [32:58]

Yeah, thank you. I think that’s a good question, right? If you get all three of these drugs up front and you’re a candidate for one of the other drugs later on, what we don’t know, and this trial didn’t answer for us, is if you give two drugs and then move on to two drugs later, is that equally as beneficial than giving all three drugs up front? And that’s always a question we don’t have the answer to.

I guess what I would say to that is we need more research to figure that out. Yes, if you have these three drugs upfront and they stop working as well as we want, we’re not going to probably, necessarily give you two of these drugs next, right? So yes, that is true.

But we’re also always coming up with new ways to attack cancer and new treatments. So I don’t like to not give patients a therapy I think is really effective up front, because you never know if we get another line of therapy, because someone may not live long enough to get another therapy later on down the road.

So I don’t like to save things for later. I like to use all my good drugs as soon as I can.

But in this situation, the three-drug regimen comes with a whole lot more side effects and is it equally as beneficial to just give two drugs upfront and then give the third drug later on and you still get the same benefit and fewer side effects? I think we don’t know the answer to that question yet, but other studies will help us address that.

I think that’s really a good question to ask and we’re just not quite there yet. But I do think this treatment’s not going to be for everyone. Alpelisib or capivasertib, there are side effects — rash, diarrhea, high blood sugars — and not everyone can tolerate them and some need to come off. But I think that it’s worth giving it a try.

In terms of triple-negative breast cancer: Drugs that target this pathway, the PI3K pathway, have been investigated with really not positive results. These drugs are not approved for triple-negative breast cancer but there have been trials looking at similar types of drugs with chemotherapy for triple-negative breast cancer. I don’t know that this drug that targets a PI3K alteration is going to be beneficial in that setting. And I’m going to try to get to some data hopefully that while the studies that were presented maybe weren’t necessarily for triple-negative breast cancer, some of these drugs are being investigated for triple-negative breast cancer.

Rita Nanda, MD [35:54]

Getting back to HER2-positive breast cancer, again, for those of you out there who have it or know people who are living with HER2-positive breast cancer, there was another study looking at Enhertu. Right now Enhertu is approved for HER2-positive breast cancer and as we talked about triple-negative breast cancer with HER2-low and then hormone receptor-positive breast cancer with HER2-low disease and potentially ultralow as well coming down the line. So there was a study that was looking at adding Perjeta, or pertuzumab, to Enhertu.

Enhertu is basically Herceptin but with chemo attached to it. If we have Herceptin and Perjeta and then the chemo attached to the Herceptin, could that potentially be better than just the Enhertu alone? That’s what this trial was looking at. Looking at patients with HER2-positive breast cancer and patients were randomly assigned to Enhertu alone or Enhertu with Perjeta.

What this trial found is, now Enhertu alone does an amazing job for HER2-positive breast cancer. Basically three quarters of patients, so 76% of patients, respond to Enhertu alone. But response went up even higher when Perjeta was added to the Enhertu. So response rates were, you know, about 85% here. The vast majority of patients did have a response to this therapy. And when we looked at how long the cancer remained under control, what you can see is that, looking at the 1-year time point of starting this therapy, 90% of patients who got Enhertu plus Perjeta still had their cancer remain under control and it was about 80% of those patients with the Enhertu alone.

So we could take an extra 10 out of a hundred patients and have their cancer remain under control by adding Perjeta to the mix.

Now this is not ready for primetime even though Enhertu and Perjeta are both approved. But I think that we’re going to be seeing a larger study looking at potentially adding Perjeta to Enhertu for women with HER2-positive breast cancer. And I think that this is going to be studied in the early-stage setting as well because if we can do this for women with early-stage breast cancer and not give all the therapy that we’re giving now and cure more women and prevent these recurrences, I think that would be really exciting for women with early-stage, HER2-positive breast cancer.

As I’d already mentioned before Enhertu is already being studied in the early stage setting by itself or with immunotherapy for women with triple-negative breast cancer as well as hormone receptor-positive breast cancer.

There are also studies ongoing looking at Enhertu by itself in early HER2-positive breast cancer. But whether or not this strategy is going to also make it to the early-stage setting, I think, remains to be seen. But it’s looking very promising in the metastatic setting.

This drug, Enhertu, drugs of this category, these antibody-drug conjugates are being studied for all the different types of breast cancer and early stage as well as in the metastatic setting. So really exciting times for all different patients with breast cancer, whether it’s triple-negative, whether it’s HER2-positive, whether it’s hormone receptor-positive, whether it’s early stage or whether it’s metastatic.

With that, I have time, I think the last 15 minutes, for questions across the board. I’m going to stop sharing my screen here, and I am happy to answer questions about other studies that I didn’t even talk about.

I just wanted to focus on things that you might be hearing about or thinking about or seeing in the clinic. And I just wanted to focus on kind of a few of these studies, but there was so much at ASCO this year and I know Jean and the team at Living Beyond Breast Cancer has some questions for me. And then also whatever you all who are listening in have, I’m happy to take those questions.

Jean Sachs, MSS, MLSP [40:18]

Thank you so much. This has been so helpful, and everybody’s really appreciating it.

I just want to ask a few questions around side effects. because these new therapies are, we know they’re, game changers for some people, but they do come with side effects. Specifically around the CDK 4/6 inhibitors, Kisqali in particular, that some people have a really hard time managing the diarrhea. So any insights you have?

Rita Nanda, MD [40:45]

Yeah, I mean I have to say in my practice the Verzenio is usually the worst for the diarrhea. Kisqali and Ibrance are usually a little bit better. Ibrance and Verzenio usually cause a little more low blood counts, so neutropenia and things that people struggle with, whereas the Verzenio is a little bit more diarrhea.

However, everybody’s different and all the drugs are different. We have three drugs in this group. And so for my patients who struggle with one side effect, sometimes I’ll try another drug that may not have as much of that, but if someone’s having diarrhea, if someone’s having low blood counts, generally what I do is decrease the dose first, and that is the first thing that we do. All of these drugs have three different levels of dosing and we can continue to reduce.

Sometimes I’ll break it up. The Verzenio and the Ibrance are designed to be given 3 weeks in a row, 1 week of a break. The Verzenio is continuous, twice a day. Sometimes I’ll do week on, week off, or I’ll lower the dose or I’ll give patients a little bit of an extra break of a couple weeks before they start their next cycle.

There are all these different strategies that we can do to try to keep someone on. But if someone’s really struggling with a side effect, we need to manage those. These drugs are effective but they have to be associated with a reasonable quality of life too. Patients have to live, and the goal of helping people live longer and better is to help them live longer and better and not worse. And so there’s always a tradeoff. Some of these PI3K inhibitors I talked about, alpelisib, which is Piqray, capivasertib, I’m sorry, I can’t remember the trade name of it.

Jean Sachs, MSS, MLSP [42:32]

Is it Truqap?

Rita Nanda, MD [42:34]

Yes, thank you. Truqap. You know, they’re not tolerable for all people and you like to try them, but if somebody can’t tolerate them with dose reductions or dose delays, then sometimes we just have to stop them because life has to be, you know, good.

Jean Sachs, MSS, MLSP [42:51]

Yeah, good for the audience to just know. You have to really talk to your medical oncologist about your side effects and how it’s impacting your quality of life.

I’m going to just switch topics a little bit. There’s a couple questions about ctDNA, where are things going and what are your thoughts?

Rita Nanda, MD [43:11]

Yeah, I mean, so ctDNA is kind of a classic example of a test that we have approved and available for use. And there are many different companies that have ctDNA tests, but we don’t always know how to use them.

Some people refer to ctDNA as liquid biopsies because this is something that we can test in the bloodstream. Some current uses of ctDNA in the clinic are looking at patients’ ctDNA and trying to figure out what type of therapy to give them. So in estrogen receptor-positive metastatic breast cancer, I use ctDNA all the time because it helps me figure out who needs what type of therapy [to use]. For example, about a third of patients with hormone receptor-positive breast cancer have these PI3K mutations, about 30% to 40% can develop mutations in the estrogen receptor gene. And there are therapies in the clinic that help us, like it helps me figure out who can get Piqray, who can get Truqap, who can get Orserdu, because that is something that we can test in the bloodstream and figure out what to give patients.

So that’s where there’s already a use in the clinic that we’ve got for ctDNA.

People are also looking at ctDNA in early-stage breast cancer to figure out who’s at risk for recurrence. Because if you have ctDNA in the early-stage setting, you may be at higher risk for recurrence. It’s not definite, it’s not that if you have ctDNA you’re definitely going to recur, but there’s a higher risk of it.

We’ve seen that in clinical trials, and there are a lot of companies that are going out there to physicians saying, “Here’s our test. You can figure out who’s going to be at risk for recurrence.” And so I have a lot of patients who get these tests in the early-stage setting, but we’re not there yet to know what to do with this clinically.

So I’ve got patients who will get a Signatera test and they come to me and they say, “I’ve got ctDNA, so what do I do with it?” And we are not there yet as clinicians to know.

You know, if I scan someone and they’ve got disease that we can see, well then, you know, they’ve got metastatic disease and we know how to treat metastatic disease: We need to figure out what kind of breast cancer it is, we do a biopsy, and then we look at the different therapies that we’ve got. But if there’s a ctDNA test that’s positive and I don’t see anything on a CT scan, I don’t really know what to do. What treatment do I give? How do I follow patients? So there’s still a lot of research that needs to go on there to help us figure out how to use ctDNA in that setting.

In the metastatic setting, we have great data. Still, there’s a lot that we need to learn there too, but it can sometimes help us figure out how to use a treatment, help us figure out if a treatment’s working or not. But in the early-stage setting, it’s still an unknown.

Jean Sachs, MSS, MLSP [46:24]

OK, that’s helpful. So we have to keep following it and learning. We’re only going to have like one or two more questions.

Were there any studies about nutrition? And I believe there was a study about a plant-based diet. Not that I expect you to have read every study, but if you have anything to share that would be great.

Rita Nanda, MD [46:43]

Yeah, and I’m sorry, I am not familiar with that study that was presented at ASCO this year. But I would say in general, what we recommend to our patients is to have a heart healthy diet, and to exercise and be active.

All of these have been shown to help reduce the risk of recurrence for early-stage disease. And there are some studies around exercise that are actually showing a reduction in a risk of recurrence. I mean, these are early small studies, but being active, getting your heart rate up, eating a healthful diet — low fat, high fiber, and you can get low fat, high fiber in a plant-based diet.

But plant-based diets can also be unhealthy if you’re not eating healthful plant-based diets. Refined foods can be plant-based, but not good for you. So I think, and I’m sorry, Jean, I am not familiar with that study, I would say plant-based is fine, but I don’t think that if you eat a plant-based diet that’s unhealthy, it’s not going to be a great strategy. And if you eat a non-plant-based diet that is healthy, well then that’s a very reasonable strategy for patients to help mitigate their risk of recurrence, to live longer with metastatic disease.

I think it’s a personal decision, but I don’t advocate that patients go out and completely change to a plant-based diet if that’s not what they already are doing and want to do from a food intake perspective.

Jean Sachs, MSS, MLSP [48:17]

Yeah, and we did write about the study at Living Beyond Breast Cancer, so I think Sharon linked that in the chat if anybody’s interested.

There’s so many questions, but I think it might be helpful to end if you could do this clarifying question, because I think there’s always a lot of confusion.

Someone’s asking what tests capture ctDNA. Guardant? FoundationOne? Maybe you could explain biomarker testing and the difference between that and ctDNA testing I think would be helpful.

Rita Nanda, MD [48:50]

Yeah, so there are many different companies that have different ctDNA tests out there and it’s hard to know, is one better than the other? Every company will tell you their ctDNA test is better than another company’s ctDNA test. Some ctDNA tests get done in the setting where your initial cancer is sequenced and then they look for those same mutations in your bloodstream. And others are just a panel of mutations that they look for in the bloodstream that’s not guided by the tumor that you had either in the metastatic or the early-stage setting. And I think no one really knows which strategy is better.

There are so many different tests out there, and I would say a lot of different doctors use different tests. Some are more established than others, others are newer. But again, I think just like not knowing exactly what we do with the results all the time, it’s impossible to know if there’s a best test to use or not.

I think that if you’re considering asking your physician or if your physician uses a ctDNA assay to manage your care, that you ask them: What is it about this test that made you use it for me? How are you going to use this test for me? Why do you get a test if you don’t know how to use it just yet? And those are the questions that you should know.

You should feel very empowered to ask your doctor, you know, what test do you do you use? Why do you use it? Well this person is my friend and they told me this is a good test. You know, I mean that’s probably not good enough. What’s the data around the test and how is that test going to inform how you are taken care of? I think those are questions you want to ask. Just because you can get a test doesn’t mean you should get a test if there’s not a utility for you.

For me, I don’t get a test outside of a clinical trial in a patient unless I know what I’m going to do with the results. Because more information sometimes isn’t always better. It can just be confusing, it can cause anxiety, it can lead to mismanagement. And so I think those are all questions you should feel empowered to ask your doctor or to ask about a test and why you should do it and why maybe you wouldn’t want to do it.

Jean Sachs, MSS, MLSP [51:22]

That’s really good advice. There’s a lot out there and things are changing so quickly.