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Immunotherapy is transforming the treatment landscape for triple-negative breast cancer. Through patient cases, Drs. Ruth O’Regan (medical oncologist, University of Rochester) and Jacob Kettle (Pharmacist, University of Missouri) discuss the application of novel treatment options.

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Air Date: 8/18/2021

TRANSCRIPT

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SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

RUTH O'REGAN: Hello and welcome to ASCO's Education Podcast episode, focused on new therapies for triple negative breast cancer. My name is Ruth O'Regan. I'm a medical oncologist and the Chair of Medicine at the University of Rochester.

JACOB KETTLE: And I'm Dr. Jacob Kettle. I'm an oncology clinical pharmacy specialist and pharmacy manager at University of Missouri Health Care's Ellis Fischel Cancer Center. We'll start our discussion today with a patient case. So let's say we have a 64-year-old female diagnosed with stage two triple-negative breast cancer three years ago. She received neoadjuvant AC-T and then underwent mastectomy, followed by adjuvant capecitabine. One year after completing therapy, she presented with new neck masts. Imaging demonstrated cervical nodes, probable liver metastases, and lymph node biopsy confirmed suspicion of recurrence, and now metastatic triple-negative breast cancer that is PDL1 positive.

So Dr. Regan, what, in this patient, would you be considering for therapy for her.

RUTH O'REGAN: Yeah, so I think unfortunately this is a pretty typical history of a patient with triple-negative breast cancer having this recurrence within two to three years of diagnosis. So her cancer is PDL1 positive, so obviously that would mean that we would consider immunotherapy for this patient. And there are two options with regard to this. We can either use atezolizumab or pembrolizumab plus chemotherapy, which could be paclitaxel, nab-paclitaxel, or, indeed, gemcitabine and carboplatin.

So just to very briefly review the trials-- so the IMpassion 130 trial randomized patients in the first-line setting with metastatic triple-negative breast cancer to nab-paclitaxel weekly with or without atezolizumab, and it showed a benefit and progression-free survival of about two months in patients whose cancers were PDL1 positive, and also an overall survival advantage that was quite meaningful at about seven months in the patients who received the immunotherapy plus nab-paclitaxel compared to the control arm. So that obviously would be a very reasonable option for this patient.

The KEYNOTE-355 trial evaluated chemotherapy, which could be paclitaxel, nab-paclitaxel gemcitabine, carboplatin, with or without pembrolizumab, again in the first-line setting for metastatic triple-negative breast cancer. And so really, very similar results to the IMpassion study with about a two month improvement in progression-free survival in patients whose cancers were PDL1 positive.

What we'll talk about later on is how we define PDL1 positivity in this patient population.

JACOB KETTLE: Yeah, I think that's an important distinction.

RUTH O'REGAN: Yeah, I think we can talk about that, because I think most of us now are actually doing both of the assays. But on the face of it, in somebody who has a cancer that's PDL1 positive, I'm not sure that there's a huge difference. Obviously you can't do cross-trial comparisons. I tend to use atezolizumab plus nab-paclitaxel because that was the first one that was approved. But I also think, in a patient who's had a recent taxane, using pembrolizumab plus gem/carbo would also be very reasonable.

The other trial I was just going to mention was the IMpassion 131 trial.

JACOB KETTLE: Yeah, absolutely. It's a game changer.

RUTH O'REGAN: It really is, because in that study they use paclitaxel with or without atezolizumab and actually didn't see an advantage for the immunotherapy, even in patients with PDL1 positive cancers. We really don't know why that is, but it's definitely an interesting finding.

JACOB KETTLE: I mean, I think that really speaks to the importance of sticking with what we know from the trials.

RUTH O'REGAN: Absolutely

JACOB KETTLE: I think there's a tendency, especially with pembro's FDA approval, says chemo. Just-- that's it, chemo. But the trial, as you mentioned, limits it to paclitaxel, nab-paclitaxel, or the combination of carbo and gemcitabine, but really to extrapolate that to other chemo regimens, other drugs, I think that's a little bit of a stretch. Because, again, we saw an IMpassion 131, maybe it's not, across the board, efficacious. There may be some subtle differences there. I'm glad you brought that up, because I think that's an important distinction.

RUTH O'REGAN: It's all about following the data. I think that's a key thing. So Jake, just in your role as a pharmacist, I think will be very interesting for you to talk a little bit about toxicity of these agents, and if there's any difference in the safety profile between these agents.

JACOB KETTLE: Yeah, I think what we've seen is pretty consistent as really all our experiences. We've started combining immunotherapy with chemotherapies that really it's not this new emergence of unexpected toxicity or an unacceptable level of toxicity. It's just what we would expect with chemotherapy agents and what we've already known with immune therapy agents. So there's nothing new and emergent or difficult to deal with. And from the IO toxicity profile, it's all the same stuff we're used to. Derm toxicities, GI, pulmonary, endocrinopathies for the most part.

We are comparing to PD1 inhibitor in pembrolizumab to PDL1 inhibitor in atezolizumab, so maybe there are some subtle differences. I think some of the things I've read have suggested maybe endocrinopathies are potentially more likely with PD 1 inhibitors.

But these are all subtle things, very nuanced-- I don't think anything that would really dictate a difference in choice of therapy. So I think from the side effect profile, fairly interchangeable, at least from the immunotherapy perspective. Obviously, we're talking about the biggest difference is the chemo backbone, and that's going to be a key driver in what regimen you pick.

Again atezolizumab-- very limited to the nab-paclitaxel backbone, which is great drug. Like you said, it was the first out. And I think another important caveat is that is the only trial in this space where we have overall survival data. We don't see that yet in KEYNOTE-355. Although, as you pointed out, PFS looks very similar between the two. So we anticipate-- don't extrapolate too much, but anticipate those are, efficacy-wise, pretty interchangeable.

But the chemo backbone-- big difference between the two. Again, you have a little bit of flexibility of pembrolizumab to use paclitaxel, nab-paclitaxel. Or I think, again, for those patients that have recently exposed to paclitaxel-- it kind of fits with our case. This patient-- relatively early relapse, pretty early recently exposed to taxanes in the neoadjuvant or adjuvant space, you may want to use a different regimen. Carboplatin and gemcitabine-- a great commonly used triple-negative backbone, especially again, if you have those folks with more disease burden, visceral disease, where you want to get that bigger punch up front. I think that's another potential role there.

But one other thing is to talk about logistics. These kind of regimens are very different because of how the immunotherapy is dosed. So when we use atezolizumab with nab-paclitaxel, that aligns very nicely with a 28-day cycle. Atezolizumab on day 1 and 15, nab-paclitaxel on day 1, 8, and 15. An off day at 22 that flows really nicely. Pembrolizumab, when you combine it with carbo and gemcitabine, that aligns really nicely with the 21-day cycle. Again, pembrolizumab on day 1, carbo, gem, day 1 and 8 and off day of 15.

The regimen that gets a little funky, for lack of a better word, is when you try to combine pembrolizumab with the taxane, because the taxanes kind of line up on a 28-day cycle, days 1, 8, and 15. And pembrolizumab is a 21-day cycle. So that could become a little bit cumbersome to navigate those waters and get those doses the right days. So you can just, from a logistical perspective, I think there's some differences there. And the challenge really is, how do we kind of get this nice balance of finding the treatment regimen that's compatible with the patient's lifestyle, the monitoring frequency, and just your clinical operations to make sure all those things align?

And we do want to have some flexibility. I think that's one of the great gifts in modern oncology, is we have all these good choices, but both are really important. You also want to have some consistency. So anyway, that's a really long-winded answer to side effects. I don't think there's much difference, in terms of side effects.

RUTH O'REGAN: I think your point is very important. Because this is all about the patient, of course. Because we've got metastatic triple negative breast cancer. So I think making it as painless as possible for them to come in, as far as their scheduling, I think, obviously, is very important.

Now, I think one of the issues with the immunotherapy is that I don't think we got great biomarkers. So we use PD-L1, but really, it's imperfect. And as we kind of alluded to earlier in the IMPASSION study, they used PD-L1 on the immune cells as a marker, and about 40% of the cancers in that study were determined to be positive. And that's where the benefit was seen.

In contrast, in the KEYNOTE study, they used what I think a lot of, outside the breast cancer world, is being used a lot, is this CPS, or Combined Positive Score, that basically looks at the PD-L1 positive tumor cells and immune cells and basically looks at them compared to the overall number of tumor cells. So at this point, we're kind of in a situation where we have to kind of check for both.

The interesting thing that's been shown is that there's not complete overlap. It's only about 75%. So it is possible that you could have a cancer that was PD-L1 positive by one of the assays, but not by the other. And I guess that might help us decide which agent to use, although I've never seen that myself in my practice. But I don't know what your experience with that is. It would be nice to have a better biomarker, I think.

JACOB KETTLE: Yeah, I'm glad you brought that up. Because I would be in the same boat. I haven't seen a case, but obviously it's possible to have some discordance. And we're looking at PD-L1 expression, whether you're looking at the tumor, or you're looking at expression in a combined positive score, regardless of the assay, it's on a scale. It's not a yes or no question. And little, subtle differences can be the make or break between determining whether someone's PD-L1 positive.

I've heard-- and I don't want to comment too much-- but there could be discordance whether you're testing archived tissue, whether you're testing metastatic tissue, maybe some differences between what site the metastatic disease was found in. Did you find it in the liver? Did you do the biopsy from the lymph node? Again, that all speaks, it goes back to the imperfection of PD-L1 as a biomarker. It's just kind of this dynamically unstable marker that's not as predictable and not as viable as some of the other biomarkers we use. And we want to take advantage of it as much as we can, and find as many unique treatment options for patients, but also don't want to leave-- we don't want to leave anything on the table.

RUTH O'REGAN: And I think the other interesting thing that we'll talk about later is that PD-L1 doesn't appear to be a biomarker at all in the earlier stage setting, which is, I think, very interesting. I think one of the things that's worth mentioning is that, of course, some patients do incredibly well with immunotherapy and have very, very prolonged responses. So trying to work out who those patients are, I think, would be just incredibly valuable. I have a couple of patients that actually came off the immunotherapies because of immune toxicity, but have remained, really, in remission for years after that, even though they actually weren't even receiving the drug. So it's really fascinating.

I think the other thing, though, is unfortunately, the majority of patients do not have cancers that are PD-L1 positive. And I guess the question is, what would we do for those patients? And the only really standard is chemotherapy. And I guess I'd be interested in your thoughts on, is there a preference first-line chemotherapy that would be used in your practice, or what are your thoughts on that?

JACOB KETTLE: I'd more defer to you on answering that. As far as our practice, you kind of have the whole mix of what you can pick from. You've got taxanes. You've got anthracyclines. You've got gemcitabines. We've got capecitabines of the world. Eribulin is a fantastic drug. Again, a lot of that goes back to what's best for the patient. And I think that is, again, the miracle. It's a challenge, because we all of a sudden have all these options, but it's the great blessing in practicing in oncology today, is there is this wealth of options, and we have the potential to really guide therapy to what's preferential to the patient.

RUTH O'REGAN: Yeah, I completely agree with that. And my thought always has been-- and I think this is very much in keeping with the NCCN guidelines-- is that there isn't a huge difference, in terms of efficacy. So I actually quite often use capecitabine in these patients, even though there was some data at one point saying that maybe capecitabine wasn't as effective in ER-negative breast cancer. I think we know that's not true in actual fact. So I think that's a great option.

If they haven't had a taxane, either paclitaxel or nab-paclitaxel is a good option. And then I think if somebody's got a large burden of disease, using a doublet like gemcitabine and carboplatin is totally reasonable, as well. Obviously, thinking about clinical trials, and particularly once you get past the first line setting for these patients is very important.

And I think one of the complexities about triple-negative breast cancer is the fact that there's at least four different subtypes that probably do require slightly different approaches. But at this point, that's not really standard of care. We kind of just manage them all the same way. But I think that's what's kind of on the horizon, as far as selecting at the best option for patients.

I think one very interesting subset is the subset that expresses androgen receptor, and which I think initially, we were super excited about. And I still think it's very interesting, but so far the data looking at antiandrogens in these cancers has not been that impressive, although there are some patients that benefit.

JACOB KETTLE: Well, I do think, too, the immunotherapy story, we kind of got talking about biomarkers. Even if you're not PD-L1 positive, even if the tumor doesn't express PD-L1, that's not necessarily the end of the role of immunotherapy in breast cancer. KEYNOTE 119 showed that pembrolizumab monotherapy later on didn't work, but we still need to be assessing for tumor mutation burden, microsatellite instability or mismatch repair. Those are other avenues by which we do have some good data to support that there is a role for immunotherapy in breast cancer, these triple-negative breast cancer patients.

Like you said, only about 40% are going to be PD-L1 positive. So that leaves 60%, more than half the pie, that are going to not have a route for immunotherapy. So I do think it's important that we always explore tumor mutation burden and microsatellite instability. Because again-- and you've alluded to this-- the great promise of immunotherapy is this potential for really long, sustained responses. And until we have really good predictive tools to find exactly what patients are going to be that, I think we should be striving to at least offer that glimmer of hope, that potential opportunity to as many patients as we can. But I think it's another important part of breast cancer is that, again, immunotherapy doesn't start with PD-L1. That's just a sliver of the useful biomarkers here.

RUTH O'REGAN: I completely agree with that. I think for our patients, it's important to consider sending tumor genomics, for sure, for exactly the reason that you said. I'm obviously also doing genetic testing to see if they've got a BRCA1 or BRCA2 mutation, or indeed a PALB2 mutation. Now there's some data suggesting that PARP inhibitors might actually be effective with those germline mutations as well. So I think definitely, sending that off makes sense.

Unfortunately, as we know, in triple negative breast cancer, we don't very often see actionable mutations. We see them, I think, more commonly in ER-positive breast cancers. But certainly we're ascending, I would think.

JACOB KETTLE: Excellent. I think that was a great discussion. Let's shift gears and do a second case and talk a little bit about this emergence of immunotherapy in the upfront setting, in the neoadjuvant setting. We'll talk about that a little bit, and then what are some additional later-line options?

So we'll do our second case. This will be a 45-year-old female presents with relapsed/refractory triple-negative breast cancer, metastatic disease in the bones and liver. Her initial therapy consisted of neoadjuvant chemotherapy combined with immunotherapy. And that would be what was discussed in the KEYNOTE 522 trial. So before talking about choice of therapy for this patient, let's dive in a little bit about and talk about KEYNOTE 522. What are your thoughts of up-front immunotherapy in triple-negative disease?

RUTH O'REGAN: So KEYNOTE 522 took patients with earlier stage triple-negative breast cancer and basically randomized into the standard anthracycline taxane-based chemotherapy with or without pembrolizumab, and actually showed pretty impressive pathologic complete response rate in the immunotherapy arm. It's about 65%, and it was quite a bit higher than the control arm, where it was about 50% or so. And they actually have some data as well looking at event-free survival showing a benefit for the addition of pembrolizumab.

It's not FDA approved yet. And obviously, you have to take into account toxicity, which I'd certainly like to get your thoughts on. But I think we know that pathologic complete response is very important, a prognostic factor in triple-negative breast cancer, at least in most subtypes. So getting a pathologic complete response rate that high, I think, is very important. And I have to say, I tend to reserve this approach for patients who have clinically node-positive breast cancers or locally-advanced breast cancers. Because-- I should have said this earlier-- because in KEYNOTE 522, all the patients got carboplatin as well. And that's one of the problems, I think, because it's hard to add carboplatin with paclitaxel.

Just to mention that we also, at ASCO, just heard a follow-up of the GeparNuevo study that looked at durvalumab with a slight, somewhat similar anthracycline taxane-based regimen. They saw a higher pathologic complete response rate in the durvalumab arm. But actually, we're showing data, now, on longer-term outcomes, and again showing a benefit for the immunotherapy.

So it is interesting. I think you're always weighing up longer-term toxicities with the efficacy seen here. But I think with a pathologic complete response rate that high, I think in a patient who has more higher-stage triple-negative breast cancer, I would consider adding pembrolizumab for that patient in this setting. But I guess I'd like to hear your thoughts on weighing up toxicity. It's a little bit different in this scenario versus the metastatic setting, I think.

JACOB KETTLE: I completely agree with you. That PCR rate is supremely promising. Obviously, we need time for the data to mature. But I think there's definitely a subset of patients that I think we're going to find this, hopefully, to be very beneficial. And triple-negative disease is problematic, so any additional tool is useful. But again, it's a very intense chemotherapy backbone.

Four cycles of carbo-paclitaxel, and then four cycles of an anthracycline and cyclophosphamide base with pembrolizumab throughout the whole cycle, that's not going to be something that all patients are going to be able to tolerate. So again, as the data matures, my hope is that we can really narrow in on the subset of patients that this is most likely to really deliver a lot of benefit to. And I've probably said this three or four times already, but I really didn't feel like this is the great promise. But again, the great challenge of oncology practice today is, we're going to end up with four or five different great options for up-front therapy in neoadjuvant or adjuvant treatment, and it's really going to be up to us to really tailor therapy and find this ideal balance of risk and benefit ratio to meet patients' needs, and what they value.

And so some patients may have, they want to avoid the severe toxicities at all costs. And that's maybe how we pursue, is to get the best benefit with that in mind. And then you'll have patients that will say, I'll go through anything. I want my risk of relapse be absolutely as low as possible, and I'll take all the chemo you're willing to throw. And trying to figure out how to walk that line, I think, is our challenge.

So with that in mind, remember back to our case, our second case here, we're going to assume that this patient's relapsed after immunotherapy in the front line. And I think that is another thing we'll explore, as the years go by, is learning, what do we do when we start seeing these therapies early in treatment, whether it's breast cancer or other tumor types? But what would your approach be, if they did relapse after initial immunotherapy?

RUTH O'REGAN: Well, I think this is a data-free area. And I should have said when I was talking about the earlier phase studies that PD-L1 is not a biomarker in that scenario. So if we assume this patient has PD-L1 positive cancer, I guess it would really depend on how long it was since she got the neoadjuvant chemotherapy. But I could envision if she was a couple of years out, I might think about rechallenging her, particularly with a different PD-L1 or checkpoint inhibitor. But I think that's not the likely scenario, because most of these patients will have pretty high-stage disease when they present, and they probably relapse pretty quickly.

So I guess we're kind of back to the case we talked about earlier, where you're really looking at the different chemotherapy options. So I think there is a potential for rechallenging with immunotherapy. I don't know-- and you may know this-- if there's any data outside of breast cancer, like lung cancer, where this has been done, for example. I'm just not aware of that data.

JACOB KETTLE: Yeah. I'm not aware of any really solid evidence. I think you can find anecdotal reports or some retrospective studies that do suggest maybe it's beneficial. And I think, especially like you mentioned, for someone with a nice long response, good, strong tolerability, all those kind of things, may be worth considering.

But again, the challenge with immunotherapy, it doesn't work quickly. So you always have that component. And like you said, these are aggressive, rapid relapses. That may not be something you can lean on too heavily. So I think it all speaks back to, we're very confident in pathological complete response as a very strong surrogate marker for long-term benefit. But again, we're using it in a slightly new space.

And until that data is very mature, and we have the overall survival data, what we don't know is, how does this all translate to the whole picture for the patient? If we burn out of immunotherapy up front, I don't know. Does that mean it's not useful, and we've lost lines of therapy in the relapse/refractory setting? I don't know. Those are some of the big questions we have.

RUTH O'REGAN: And I think it also speaks to what you said earlier, that the whole immuno milieu of the cancer may change, depending on what setting you're looking at. So there could be very good rationale for rechallenging with immunotherapy. But again, I think this is an area where we really would need some data for sure.

JACOB KETTLE: Yeah, absolutely. Very tricky. So let's play out the scenario just a little bit more. Let's say we started carboplatin and gemcitabine, for instance, in this patient. She got about nine months of therapy, and then progressed again. What other, maybe, newer options are lingering out there for sort of later-line triple-negative metastatic disease?

RUTH O'REGAN: So unfortunately, of course, that's typically what you see. They usually, patients usuallt experience disease progression within six to nine months. And so obviously, alternative chemo options would be on the table, a taxane, if she hasn't had one recently, capecitabine, if she hasn't had that. However, I think for a patient like this, I would strongly consider sacituzumab, which is a relatively new antibody drug conjugate that targets Trop-2.

The data from the ASCENT study, which looked at patients with triple-negative breast cancer who'd had at least two prior lines of treatment were randomized to sacituzumab or to physician's choice of chemotherapy, and the data was pretty striking. And the progression-free survival, it was less than two months in the control arm, versus six months in the sacituzumab arm. But the overall survival was doubled from six months to 12 months by using sacituzumab. So that's pretty impressive in this scenario.

And it appears that, although most triple-negative breast cancers do express Trop-2, there doesn't appear to be a definitive correlation between Trop-2 expression and benefit from this drug. So there appears to be some kind of a bystander effect from this antibody drug conjugate. I think it's a really interesting drug, and maybe you can talk a little bit about the tolerability of it.

JACOB KETTLE: Yeah. So again, like you said, it's a Trop-2 target. That's the antibody component. And Trop-2 is a transmembrane glycoprotein. It's upregulated in a lot of tumor types. So this is not something that you necessarily would do additional testing for. It's not unique to breast cancer. And sacituzumab-govitecan has an approval now in bladder cancer as well. So I think we're going to start seeing more emergence and utilization of Trop-2.

And then like you said, it's kind of an enriching biomarker. You might see a slightly higher response rate for those overexpressors. But again, low expressors still respond. But I think when it comes to the side effect profile-wise, it was all driven by the chemo payload. And that's Govitecan, or SN-38. This is the active metabolite of irinotecan.

And so a couple of things make this really exciting to utilize in breast cancer. One is, we're all probably fairly familiar with managing the common side effects of irinotecan, predominantly neutropenia and diarrhea. So we don't have to relearn or come up with a new kind of management profile, side effect-wise. But I think part of why we see such a robust response is this is a mechanism of action. Govitecan, it's a topoisomerase inhibitor that almost, I'd say, the vast, vast majority of breast cancer patients have not been exposed to that mechanism at any point in their treatment journey. So you take advantage of that new option.

And I think, all things considered, this is why we've seen this kind of recent-- it's not brand new technology-- but we've seen this recent emergence of a lot of antibody-derived conjugates. Because it really does allow you to take advantage of antineoplastic agents that may otherwise be too toxic, but we find a way to deliver it in a very sophisticated, precise manner. And by doing so, again, we're able to take advantage of chemotherapeutic agents that otherwise would be on the shelf. But we can deliver it in a very precise way. And so that's a really exciting piece of the promise for this drug. And again, just to ask you, do you any anecdotal experience or insights with the drug?

RUTH O'REGAN: Yeah. I've used it a little bit. I actually started a patient on it today. But overall, I think it's well tolerated. It's unfortunate it causes alopecia, obviously. But I think most patients with the results of the ASCENT trial, they're OK with that, I think. And the tolerability seems to be very reasonable.

JACOB KETTLE: I mean, a six-month OS improvement at this stage of the game is pretty clinically meaningful.

RUTH O'REGAN: I don't think we've really seen that before, actually, and so it definitely is. I agree with you completely. I think antibody drug conjugates are really the way forward, because they're so much more tailored to the cancer than regular chemotherapy. The other drug, I think, that will be interesting to see in triple-negative breast cancer is trastuzumab-deruxtecan, which obviously is approved for HER2-positive breast cancer, but again, also has a bystander effect. And there's some data from one of the DESTINY studies basically showing activity in cancers that have low expression of HER2. So I think that's going to be very exciting.

So I think there's a lot of exciting things happening in triple-negative breast cancer. There's a lot that I think we have to learn. I mean, biomarkers are going to be very important, particularly for immunotherapy. Do you have any other thoughts on other agents you're excited about in this setting?

JACOB KETTLE: I'm always fascinated by precision oncology. And like you said, I haven't really found a lot of great targets for triple-negative breast cancer. It's tended to hold out its negativity. It doesn't have-- not as if we're finding a bunch of things. So I hold out hope, just that we come across a good marker, something else targetable for these folks. I share with you the enthusiasm about trastuzumab-deruxtecan, and how it might play a role in HER2 low. Interestingly enough, that's also a topoisomerase inhibitor type, very similar backbone, chemo-wise.

But also just watching the IO story continue to play out, I think it was interesting just that breast cancer, really, especially the most common cancers, was really one of the last disease states to really see indications for immunotherapy. So just excited to see that story continue to unfold. And hopeful, always remain hopeful that we continue to push the needle forward, bit by bit, day by day.

RUTH O'REGAN: I completely agree, and that was a great discussion. So that's all we have for today. I want to thank you, Dr. Kettle, for a great conversation. And thank you so much to all our listeners tuning into this episode of the ASCO Education Podcast.

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