Trodelvy Offers Benefits for Hormone Receptor-Positive Breast Cancer

This podcast is made possible by Lilly. 

Jamie DePolo: Hello, thanks for listening. Dr. Hope Rugo is professor of medicine in the division of hematology and oncology at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, where she is also the director of breast oncology and clinical trials education. Dr. Rugo is also a member of the Breastcancer.org Professional Advisory Board. She is a principal investigator of a number of clinical trials and has published hundreds of peer-reviewed papers.

At the European Society for Medical Oncology Congress 2022, Dr. Rugo presented results from the TROPiCS-02 trial, which was looking to see if the targeted therapy Trodelvy could offer more benefits for people diagnosed with previously treated metastatic hormone receptor-positive, HER2-negative breast cancer than chemotherapy. Currently, Trodelvy is approved to treat previously treated, metastatic triple-negative breast cancer. She joins us to discuss the results. Dr. Rugo, welcome to the podcast.

Dr. Hope Rugo: Thank you so much for having me.

Jamie DePolo: So, before we get to the results, could you just briefly explain to us what Trodelvy is and how it works?

Dr. Hope Rugo: Absolutely. This is a really exciting area right now in the treatment of really all cancers, but we of course had remarkable data in the last few years for breast cancer. The class of drugs are called antibody-drug conjugates, and the basic construct is an antibody that’s directed to a receptor that’s expressed more highly on a cancer cell than a normal cell. 

Then there’s a linker, and this linker — actually, it’s really interesting, you can’t tell now, but it took decades to evolve these linkers that could be digested selectively in the tumor cell. So, they have to be stable in your blood, but in the tumor cell be digested by enzymes that might be increased in the tumor, and that’s taken a long time. 

And then, there’s a payload. So, basically, the antibody, and then this payload stuck on with the linker that’s stable in your blood, could be digested in the tumor cell, and that payload has to carry a big bang for the buck. So, the payload has to be active at what people refer to as nanomolar concentrations, but we don’t know that it needs to be exactly that. It just needs to be, really, a potent drug at very low concentrations. 

And then, what happens is, the receptor has to be something that when an antibody binds to that receptor on the cancer cell, that it actually brings — it’s a fascinating process — it brings the antibody-drug conjugate complex into the cell. So, basically, the receptor is internalized. It’s then digested. These proteases or enzymes in the cell digest the linker, and release the toxin. 

So, the first generation of antibody-drug conjugates, this worked really well, but it only worked in cancers that had a very high expression of the receptor that you targeted the antibody to. But the new generation of antibody-drug conjugates has linkers that are more easily digested in the cancer cell, and then it has membrane-permeable, or hydrophilic — can be soluble in water — toxins that can leak out of the cancer cell and kill nearby cells, which, this bystander effect.

So, basically, we have a new way of delivering toxins, or a chemotherapy, that’s more tumor-specific. So, although these are chemotherapy agents, there’s no argument that they have chemotherapy-like toxicity, but they have less toxicity and less cumulative toxicity than naked chemotherapy drugs, and you’re directing the toxin more to the cancer cell.

Jamie DePolo: Thank you. So, I’m going to use an analogy, just to make sure I’m understanding. So, it’s almost like, these kinds of medicines are almost like a smart missile or a smart bomb, because they have the proteins in them, if that’s the right term, and they attach to the cancer cell, and then they release the chemo into the cancer cell without necessarily affecting the whole body like traditional chemotherapy does.

Dr. Hope Rugo: Well, you know, that was our idea when we had trastuzumab emtansine, referred to as T-DM1, for HER2-positive disease, but that’s actually not really the case now. I used that term, smart bomb, a million times, and it’s not so much the protein, but the antibody, these monoclonal antibodies, that attach to the receptors that are generally protein-like on the cell surface. 

But the smart bomb idea was that you would only target the cell that had that high expression, a HER2-positive cell. And in fact, T-DM1, and even the naked antibodies like trastuzumab, they didn’t work in HER2-negative or HER2-low disease. But these newer ADCs seem to, they do actually leak out, so they’re not as smart, right?

Jamie DePolo: It’s a sort of smart bomb?

Dr. Hope Rugo: Yeah, it’s a very smart way of using this technology to also kill nearby cells, or to kill cells that have a lower expression of your target. So, in the case of, say, sacituzumab govitecan [brand name: Trodelvy], the idea is that the antibody is a Trop-2-directed antibody, and Trop-2 is a receptor. It sends signals into the cancer cell, and it’s been linked to worse outcome in cancers, and you see this receptor on a lot of cancers, about 80%, but we know that the expression varies a lot. 

So, these newer ADCs need to work regardless of the degree of expression. The other ADC, which has now had regulatory approval not just in HER2-positive, but HER2-low disease, trastuzumab deruxtecan [brand name: Enhertu], or T-DXd, that one also has this bystander effect. And that’s really where they coined the term bystander effect. But I believe it’s an important mechanism of how these drugs work overall.

Jamie DePolo: Okay. Okay, thank you. So, now, moving on to TROPiCS-02, there were three presentations, I believe, you made one of them, about the various results from this trial. So, could you summarize the results? I knew you presented overall survival results, which sounded very promising.

Dr. Hope Rugo: Yes, so, sacituzumab is a Trop-2 antibody-drug conjugate. It’s linked to a class of chemotherapy agents called topoisomerase I inhibitors. They block an enzyme that’s important for cell survival. There’s actually a chemotherapy drug called irinotecan that had some efficacy in breast cancer, is approved in colorectal cancer, for example, and this is the active metabolite of irinotecan that’s the payload, SN-38. 

And we already, as you mentioned, know that this is very effective in triple-negative breast cancer, and there are studies evaluating sacituzumab earlier in the course of treatment of triple-negative breast cancer that can’t respond to immunotherapy, and also in combination with immunotherapy to try and further improve outcome. There’s also trials going on in early-stage triple-negative breast cancer as well. 

But in the initial studies that evaluated sacituzumab govitecan, we saw activity in hormone receptor-positive, HER2-negative, metastatic breast cancer that had received many prior chemotherapy treatments for metastatic disease, where response was in the 30% range, and also, the amount of time that the disease was controlled was also quite impressive. So, patients’ cancer stayed controlled for a longer period of time than we normally see in these later-line chemotherapy settings.

So, TROPiCS was designed to evaluate the efficacy of sacituzumab in those patients. Patients were required to have received at least two, but not more than four, lines of chemotherapy specifically for metastatic disease, and it was a homogeneously treated population, which is important. Everybody had to have received a CDK4/6 inhibitor, and that’s important, because what we’ve seen is that in patients who receive these remarkably effective targeted agents given with endocrine therapy, although patients live longer who have had CDK4/6 inhibitors, the cancers are relatively more resistant to subsequent lines of treatment.

So, we wanted to have this be a real-world population. Everybody had to have that CDK4/6 inhibitor. And what we’d already shown was that in the patients who’d received a median of three lines of prior chemotherapy, almost everybody had disease in viscera — so, liver, lung, et cetera — which we call visceral involvement. And interestingly, in this patient population, so different from triple-negative disease, the median duration of time from diagnosis of metastatic disease until randomization was four years.

We know that patients now with hormone receptor-positive metastatic breast cancer that the median survival is longer than five years, but it’s not a lot longer. So, these patients have already had four years. So, we really needed to know how long we could help patients live in this situation, and if we could prolong survival, because we know that the options for chemotherapy after you’ve received a median of three lines of chemotherapy for metastatic disease become narrower and narrower, and the drugs work less well. And we’re dogged by cumulative side effects that make it really hard to treat patients. 

So, patients were randomized in this setting to receive sacituzumab or a treatment of physician choice, which is a menu of chemotherapy, and in this patient population — most of whom who had received prior capecitabine — about 50% of patients received eribulin, a very effective chemotherapy agent. We had shown at ASCO ’22, and now published in the Journal of Clinical Oncology, that progression-free survival was significantly longer in patients who received sacituzumab.

There was a question about the median difference, which was just 1.5 months, but that was really due to the fact that a lot of patients’ cancers progressed in the first two months, regardless of the treatment arm, because the cancers were just very resistant to treatment. But when we looked at six, nine, and 12 months, we saw that there were more patients who were alive and free from cancer progression at all of those time points. And at 12 months, what was impressive to me was that three times as many patients were alive and without disease progression.

The statistics for these studies are so complicated. It really is wild, and as oncologists, we’re always kind of like, how did we come up with that idea? But now, a lot of studies are using what’s called a statistical hierarchical design, where each endpoint before has to be significantly better with the experimental agents before you can look at the next endpoint. So, the first endpoint was progression-free survival, that was significantly greater. So, then you could look at overall survival.

At the first endpoint that we presented at ASCO, there were not enough events for overall survival. And so, although it was numerically longer in patients who’d received sacituzumab, it wasn’t significantly better. But at the second interim analysis that we presented at ESMO, we had almost 400 events. And it’s important to keep in mind, when you’re thinking about the number of patients who are randomized, there were 543 patients randomized, there were 390 survival events.

So, this is a much more mature analysis of understanding what happened to patients in the natural history of their metastatic breast cancer. And what we showed at this analysis was that overall survival was significantly longer in patients who received sacituzumab, a very encouraging result. The median difference was 3.2 months, but the absolute numbers were 11.2 months for the chemotherapy and 14.4 months for sacituzumab, and this was a highly significant difference.

When we think about the percentage of patients who are alive at 12 months, that’s also, to me, a very important endpoint in thinking about what I tell my patients and how I can treat my patients most effectively, and it was 47% for chemo and 61% for sacituzumab. So, that was really important, because we had survival benefit, we looked at response, clinical benefit rate, duration of response. Those were all greater with sacituzumab, and the only complete responses were actually seen with sacituzumab.

We looked at quality of life, and we saw a significant delay in deterioration of global health status and quality of life, as well as fatigue, with sacituzumab compared to treatment of physician choice. And we looked at a number of different patient-reported outcomes, different subset analyses in the presentation by my colleague Aditya Bardia, and we saw in that analysis as well that there were really a delay in deterioration in almost all of the different factors that we evaluate that could be important to our patients, all these different functional scales and symptom scales, they are called.

And the only one where sacituzumab was a little worse was diarrhea, which we generally can manage pretty well with delay in treatment and dose reductions, as well as anti-diarrheal therapy. And interestingly, it’s definitely a patient population that I don’t see as much, because I don’t see as much diarrhea, but there’s probably differences between different patient populations in that toxicity. 

We did look at safety again as well, and safety is so important when we look at these new drugs, because you’ve got to sort of weigh the safety against the benefits, and we didn’t see any new safety signals. The primary issues are neutropenia, and as I mentioned some diarrhea, but neutropenia is just so incredibly important to monitor, to understand, and to treat proactively in patients receiving this antibody-drug conjugate.

Jamie DePolo: Okay, and neutropenia, I just want to clarify for anyone listening, that’s low white blood cell count. So, that increases someone’s risk of infection, correct?

Dr. Hope Rugo: Well, so, it’s really specific. You know, we don’t actually really care what the white count is, unless it’s below 1,000, because then we know the neutrophils are low. 

So, your white blood cells are made up of different components, and the important component is neutrophils. We know lymphocytes play some role, but we don’t really have a good handle on how to evaluate lymphocytes in patients with solid tumors like breast cancer. They seem to be more important where you’ve done a bone marrow transplant or something, and the immunity is really messed up. 

But for patients who are getting standard chemotherapy, neutropenia is a very, very common toxicity. So, not a drop in the overall white count, but the neutrophils. We used to call them polys, they’re funny little cells that fight infection more effectively than anything else. 

And it’s what’s fascinating, coming from before we had growth factors that could keep your neutrophils better, what we saw was when neutrophils were low, you also could get more mouth sores, and the mucosa or the lining of your gut wasn’t good at preventing bacteria from crossing over. So, if you have good neutrophils — and we think about this as just being 1,000 or close to 1,000 or more of the neutrophils — that then you’re protected against that kind of infection.

So, we now use preventive or prophylactic growth factors, the generic name being filgrastim, that are given as injections under the skin, and they’re incredibly effective at preventing neutropenia from sacituzumab, but also dose reduction is as well. And in patients who have a lot of so-called neutropenia, a dose reduction is an important way of managing this as well.

Jamie DePolo: Okay, thank you. So, it sounds like, if I can summarize again, just quickly, that Trodelvy was more effective, improved both progression-free survival and overall survival, and offered the same or better quality of life as chemotherapy for the people in this study.

Dr. Hope Rugo: Right. That’s absolutely right. I think that’s an excellent summary.

Jamie DePolo: In one sentence.

Dr. Hope Rugo: Well, so, I think that’s really important, because I’ve been doing this for decades, and we didn’t think that we could actually reach survival endpoints in many settings, and the only other study that looked at chemotherapy in patients who had heavily pre-treated hormone receptor-positive disease — and it was over all patients, you know? In this study, it was before we divided things up so well and understood the biologic significance of the different subsets — was a trial called the EMBRACE trial.

This trial looked at the chemotherapy drug eribulin and compared it to a menu of chemotherapy agents, and the menu was actually quite similar to what we used in TROPiCS-02. And what they saw was eribulin improved outcome and improved survival, but the median difference in survival was in the slightly under two-month range. And so then eribulin became a standard of care and got approved. And now we have a drug that’s superior to eribulin, which, you know, almost 50% of the patients received.

So, it is really a big advance in this patient population, but we have to think about that in the context of other drugs that we have available, which of course is your next question.

Jamie DePolo: Yes. Well, I do want to ask about the HER2-low cancers in this study. I know that was, again, presented by one of your colleagues on the study, and it sounds like Trodelvy is approved to treat metastatic triple-negative breast cancer. Your results showed, okay, now it can offer benefits to hormone receptor-positive, HER2-negative disease, and also, it sounds like, if I’m remembering the results correctly, Trodelvy can also help treat, now, HER2-low disease. So, if you could talk about that…

Dr. Hope Rugo: Well, so, I think I might need to talk about that, not to redirect at all, but I think we need to talk about that in the context of trastuzumab deruxtecan, and I would say it’s not also that it would treat it. It is that in hormone receptor-positive, HER2-negative breast cancer, about two-thirds of patients’ tumors have a low expression of HER2 without gene amplification. So, they don’t meet criteria for having HER2-positive disease, but they don’t have zero expression either.

And it’s important to keep in mind that our tools for looking at HER2 were all designed to differentiate positive — you can get trastuzumab — or negative, and not to differentiate between low levels of expression. So, there’s a lot of work going on trying to understand that and the discordance between different pathologists. There was a recent paper, eight pathologists looked at tumor samples, and they had a greater degree of discordance in patients who had so-called HER2-low 1+ disease versus 2+ disease. I mean, really significant discordance. 

So, you know, differentiating zero from 1+ is something that we’re still struggling with and looking at, but trastuzumab deruxtecan, as you know, demonstrated these unbelievable superiority results, comparing trastuzumab deruxtecan — I’ll call T-DXd — versus our prior standard second-line therapy for HER2-positive breast cancer, T-DM1. I mean, huge difference with a P value none of us have ever seen before. And we’re looking forward to hopefully seeing survival improvements in the next few months, potentially in an upcoming congress at the end of the year — or if not then, next year. 

So, I think that this was just a huge advance in HER2-positive breast cancer, and it’s now being tested in the early-stage setting. But when they did their initial studies with T-DXd, they also looked at patients who had low expression of HER2, and even HER2-0, because they had postulated from pre-clinical data in animals and cell lines, et cetera, that there would be this so-called bystander effect that we were just talking about.

So, the idea was, you would get a little bit of a signal. So, they did what’s called a phase I umbrella study and treated 54 patients or so, and they saw a very nice response and very good disease control, kind of similar to what I talked to you about sacituzumab, in their initial phase I study. The number of patients who had HER2-0 was miniscule, so it was really hard to evaluate, so they designed their next study to be powered to look at patients who had HER2-low that was confirmed centrally 1+ or 2+ without gene amplification, and in patients with a hormone receptor-positive disease.

And in contrast to TROPiCS-02, the median number of lines of chemotherapy was just one. Seventy percent of patients had received CDK4/6 inhibitors. About 90% had visceral disease. And so, it was a much less heavily pre-treated group of patients, and as presented at ASCO and published in the New England Journal of Medicine, they saw tremendous improvement in progression-free and overall survival in the hormone receptor-positive group.

And there was a suggestion of benefit in a sort of exploratory analysis of the 58 patients who had triple-negative disease. So, because of that data, there was a big call to look at HER2-low status and how it affected efficacy of sacituzumab. So, we went back and looked at this. Now, remember that, again, the ability to differentiate HER2-0 from 1+ is not great, but we did this centrally, of course, in the patients who were treated on TROPiCS. 

And what we found was, as you pretty much would’ve expected, in the HER2-low and HER2-0 population — so, we had a little more patients who had HER2-low than HER2-0, as, again, this is what we’ve seen. So, maybe 60% or so, 65% were HER2-low, and the rest were HER2-0, and basically, the issue was to look to see whether there was a differential benefit of sacituzumab, and there wasn’t. 

Sacituzumab was better than treatment of physician choice across all of these groups of patients for progression-free survival, and we’ll look at the overall survival in an upcoming analysis, but it was interesting. I mean, this was an unplanned subset analysis, and the sort of relative benefit was a little greater in the HER2-low than in the HER2-0, but the numbers were different, right, two-thirds versus one-third or so. So, it’s really nothing you can make anything of in unplanned subset analyses where you didn’t so-called power your trial to look at these subsets. But I think it gave us the confidence that this drug works regardless of HER2-low. 

Just talking about HER2-low briefly, about two-thirds of hormone receptor-negative and about one-third of triple-negative are 1+ or 2+ without gene amplification for HER2. And so far, we don’t know that this has any independent impact on prognosis — so outcome — outside of the fact that this tends to define a group of patients who have more biologically treatment-sensitive disease versus non-treatment-sensitive. So, we have divided our cancers — but we don’t use it clinically — into these subsets by RNA gene expression, so-called intrinsic subtypes, and there’s a group that’s more commonly seen in triple-negative disease called basal-like. And interestingly, basal-like disease is much less likely to be HER2-low. They’re more likely to be HER2-0, and we already know that’s a group of tumors in patients that don’t respond as well to treatment and for as long.

So, I think that HER2-low is fascinating. I mean, we’re using it to predict benefit of trastuzumab deruxtecan, but it doesn’t seem to have any prognostic impact by itself. So, that’s why we looked at it in sacituzumab, in TROPiCS-02, and I think that was very helpful confirmatory data. 

Jamie DePolo: Okay, thank you. I’m curious, given all the research you do, are there studies going on to more accurately separate cancers into HER2-low, HER2-0, HER2-positive? Is that something that’s being done? I mean, I know you said that it doesn’t necessarily affect prognosis yet, but perhaps if we had better tests to figure that out, would it? I’m curious.

Dr. Hope Rugo: I don’t know. I think that there’s a little bit of data from a trial called the DAISY trial that was done in France, which is fascinating. And that trial actually presented some data at ESMO ’22 also, where they — and there’s other studies that have looked at this sort of heterogenous expression of HER2-low across different sites of tumor, and across even one site of tumor. 

And so, tumors, we know, have heterogenous expression of HER2, we’ve seen that in HER2-positive tumors where you respond better to HER2-targeted therapy if you have a lot of HER2-positive cells versus very few. And obviously we’re not going to take out all of the tumors in a metastatic disease. But I think trying to look at potentially imaging ways of finding out how heterogenous HER2 expression is would be really fascinating for the future.

I don’t know if we’re going to get better tests. There is a study called DESTINY-Breast06 that’s looking at HER2-ultra-low to try and address this question. It’s over 800 patients, first-line chemo for hormone receptor-positive disease, HER2-negative, that’s looking not only at 1+ or 2+, but also at patients who just have more than zero, but didn’t quite meet a 1+. And it will be very interesting to try and see if the drug is equally effective in patients who have ultra-low disease.

Generally, people believe that it will be, and that this sort of differentiation in HER2-low is a little bit contrived, you know? And it was part of what powered the study, and it led to great results and approval, which is, you can’t argue with that, and a new treatment option for our patients. But do we really believe that patients who have HER2-0 disease aren’t going to benefit early on from T-DXd? No. 

But right now, it sort of led to a treatment paradigm or approach, which is that in patients who have HER2-low disease, hormone receptor-positive in the second-line setting, we would preferentially use T-DXd. In triple-negative disease, sacituzumab, because we have phase III data, but then, we want to understand the effectiveness of these drugs in sequence. 

And so, that’s sort of the next step in our investigations. And then, for the third of patients with the most common subset of breast cancer worldwide, we have sacituzumab govitecan as an option in those HER2-0 patients, and we of course will be looking at sacituzumab in less heavily pre-treated settings as well.    

Jamie DePolo: Okay, actually, I think you might have answered my last question, but I’ll ask it anyway. So, all this information together, if you could kind of put it in context, say I’ve been diagnosed with metastatic, hormone receptor-positive — well, actually, I’m not even going to, because it sounds like the hormone status may not matter and the HER2 status may not matter — so, I have metastatic disease. It’s previously treated. What do all these results mean for me now? 

Do I have more options? What is the sequence now? What would you tell your patients?

Dr. Hope Rugo: Well, I think, first, the subset really does matter a lot, I mean, hugely, right? So, in patients who have HER2-positive disease, there’s a separate path of treatment, and that’s really important, because HER2-positivity — 3+ by immunohistochemistry, looking at the protein and/or gene amplification — in those patients, HER2-targeted therapy is critical and makes an enormous difference on survival. 

So, if we take out that group of patients, we have patients who have triple-negative disease and hormone receptor-positive disease. In that patient population, in hormone receptor-positive disease, we’re now looking at patients, based on the recent regulatory approval in the United States, based on if they have a little bit of HER2 expression, so-called HER2-low in the second-line setting. But remember, this is chemotherapy we’re talking about, so our first treatment in those patients is sequential endocrine therapy with targeted agents — CDK4/6 inhibitors, aromatase inhibitors, fulvestrant. We’re still working on these oral drugs, like fulvestrant also was talked about at ESMO. We haven’t quite figured out the exactly right way to study them. They’re not out there quite yet. But other targeted agents are being evaluated: everolimus; alpelisib, which has toxicity issues but is still quite effective; and other agents. 

So, this is all what we do in sequence. First-line chemotherapy in, these patients tends to be capecitabine, because it’s an oral agent, no hair loss, and people have a lot of freedom. If they tolerate and metabolize capecitabine, it’s a great option. So, then we get to the second line hormone receptor-positive disease. So, we’re going to look at our HER2 expression. If it’s HER2-low, we’re going to use T-DXd. 

There is some hair loss, and one of the key toxicities, we have to manage nausea. But then this risk of interstitial lung disease, we have to be very, very careful about. Patients who have so-called ground-glass opacities on their CT scans of the chest and no symptoms need to hold [on the] drug and be treated with lower-dose steroids until it clears up. And then they can restart. Generally, we restart at the same dose, unless it doesn’t resolve very quickly. 

If you have symptoms related to pneumonitis or interstitial lung disease — shortness of breath, cough, et cetera, low oxygen — you can’t be re-treated with T-DXd, because deaths have occurred. So, that’s a really critical component. So, what do we do with patients — and I have a number in my patient population who’ve had previous pneumonitis, for example, from everolimus, or even from another chemo drug.

In those situations, those patients were excluded from the trials, but we need to monitor those patients very, very carefully and really jump in earlier. You cannot wait to get the CT scans, particularly in the first year. I don’t recommend going any longer than nine weeks for the first year, and if you did really, really well, maybe you could go out to 12 weeks. But you don’t want to wait until symptoms develop, and that’s a question that’s been asked a lot.

So, that’s what we’re doing in that patient population. In the triple-negative patient population, I would use sacituzumab, because there’s phase III data in over 500 patients with improved overall survival. 

So, now we get past that time, or we get to our patients who have hormone receptor-positive HER2-0 disease. In that patient population, I would use sacituzumab. The trial required the patients have two lines of prior chemo. Sometimes we’re a little wiggly on that and use it a little bit earlier; we see less toxicity and better efficacy. If you’re strictly holding to the trial, you would use it after two lines of chemotherapy, and in patients who have now received their trastuzumab deruxtecan or sacituzumab, depending on the subgroup, I would try the other agent in sequence. And it doesn’t have to be right after the other one, but it could be after another line of chemotherapy, because I’ve actually already seen patients who have benefited in sequence.

There’s a whole other area, which is how do we treat patients with brain metastases. We know, for example, that T-DXd has efficacy in patients with brain metastases. There are studies looking at this, and looking at it with sacituzumab govetican. So, we want to be able to use these drugs in sequence as well. 

I think it’s important to keep in mind the side effects, the low neutrophils that we talked about earlier for sacituzumab, making sure we manage the neutropenia and the diarrhea. For the patients with T-DXd, I think up-front management of the nausea’s incredibly important. Olanzapine, the antipsychotic, at low doses has been my friend, because it just works incredibly well for the delayed nausea. When you take it every night at bedtime, it helps people sleep, doesn’t have some of the other side effects that our anti-nausea drugs have. And then monitoring for pneumonitis.  

Jamie DePolo: Okay. Dr. Rugo, thank you so much. This has been incredibly informative, and I really appreciate your time.

Dr. Hope Rugo: Great. Thank you so much for your interest, and for writing this really important educational resource.