Welcome to the Breast Cancer Sessions brought to you by the Video Journal of Oncology (VJOncology).
Following an exciting day at the ASCO 2022 meeting, leading breast cancer experts get together to share their highlights. Join Paolo Tarantino and Romualdo Barroso as they dissect key updates in breast cancer, including results from the MAINTAIN trial, TROPiCS-02, as well as updates on the use of antibody-drug conjugates such as patritumab deruxtecan and trastuzumab deruxtecan.
Paolo Tarantino: So hello, everyone. This is the VJOncology Breast Cancer session, and we are very happy to discuss about the new data presented today and that is got to be presenting the next days at ASCO. Joining me, there is Romualdo Barroso-Sousa, and I’m Paolo Tarantino, and we’re going to be very happy of having this chat together and to go over what was presented. Romualdo, I don’t know if you had any idea of comments on the abstracts that were presented today on metastatic breast cancer.
Romualdo Barroso: Yes. Thank you, Paolo. I think the most important group of abstracts today were about the ADCs, the big revolution that is this new class of drugs, or at least this new wave of ADCs, and the hormone receptor-positive trials that were presented. So I think these are the major abstracts.
Paolo Tarantino: Absolutely agree with you. We’ve seen the data of T-DXd in HER2-positive breast cancer, the DB-03, DESTINY-Breast03 trial that show that T-DXd is highly effective in second line HER2-positive breast cancer, and today, we also show that the safety profile with additional follow-up was still consistent with what we have seen, especially interstitial lung disease was consistent. There was around a ten percent risk of interstitial lung disease with no grade four and five events, which was a relief. We’ve seen data, as Romualdo was alluding, in hormone receptor-positive disease and we saw data of sacituzumab govitecan, the TROPiCS-02 trial, which was a randomized Phase III trial of sacituzumab govitecan versus chemotherapy in pretreated hormone receptor-positive metastatic breast cancer patient. What was your opinion on the results? What did you think of them?
Romualdo Barroso: Yeah, so I think the data from TROPiCS were very expected, so people were interested to know what would like the data. So I think first of all, it’s important to mention what population was included in TROPiCS. So TROPiCS included a very pretreated population, heavily pretreated population. All patients needed to receive at least one line of prior hormone therapy and a CDK4/6 inhibitor, plus at least two prior lines of chemotherapy. Essentially the trial was a trial for third to fifth line, so this is a very heavily treated population. The data, the primary endpoint was met. The trial, met the primary endpoint with a hazard ratio of 0.66, that I think in the context of this setting, this particular population with bad prognosis, the trial is positive and I think it’s important. It’s important data. How about you?
Paolo Tarantino: Absolutely agree and we need more option. These are high unmet needs, and there was also an additional ADC that showed intriguing activity and was presented today, patritumab deruxtecan, an anti-HER3 ADC, which is similar in some way to trastuzumab deruxtecan. It has the same payload, the same drug to antibody ratio, but targets HER3, and this was tested in patient with all subtypes of breast cancer showing around 20 to 40% response rate, regardless of HER3 expression, which was the thing that intrigued the most. Well, did you think of this, of that no difference based on the expression of HER3? Did you expect that?
Romualdo Barroso: Yes, I think this is the first kind of data that does not show a correlation between the amount of expression and activity. I think this is the first one, maybe this is some technical issue. I think it’s premature to say that we don’t have any correlation, but for this particular trial, there was no association between the expression and the activity. This will be like the third target in this class. So HER2, TROP2 and HER3. What do you think will be the next wave and how to sequence these drugs? How would you choose for the patients?
Paolo Tarantino: This raises very important questions because of course, we are seeing so many important, so many interesting agents showing activity in both hormone receptor-positive and triple negative metastatic study breast cancer. We don’t know if a DxD base antibody-drug conjugate is going to be active after another DxD base. If we have to change the target or change the payload, and I think we definitely need prospective data to answer this question. There is a trial being designed at Dana-Farber, and we hope that it can answer this question, but of course we’re missing the most important part of the puzzle, the most anticipated data, which is the DESTINY-Breast04 trial that is going to be presented tomorrow in the plenary session. So we are not able to discuss yet the results because we don’t know them, but we know what was in the press release.
Paolo Tarantino: We know there is a progression free survival and overall survival advantage for the use of T-DXd over chemotherapy in pretreated hormone receptor-positive and triple negative breast cancer patient with low expression of HER2, and these also a very complicated setting, HER2-low. What we define HER2-low, if HER2-low is stable in time, what is the best assay for HER2-low? So what was your idea up to now with what we have. Is HER2-low, a thing like a subtype compared to HER2-zero or not? What is your idea in this setting?
Romualdo Barroso: Well, with the highlight that you are the expert about HER2-Low, but my impression based on the available data is that it’s not really a new disease, but the HER2-low is a target, a good target for a good drug that are the ADCs based on T-DXd. My impression is that we don’t have data showing that there is any difference in the prognosis of these patients based on the expression. So do you agree?
Paolo Tarantino: Absolutely agree. And I think that this, all our understanding is going to evolve with new assays. We need quantitative assays, and so dissecting all these zero, one plus, two plus is not enough here, and I really hope that we’re going to have that for HER2 and also for TROP2 and HER3. So in the end, we really need good biomarkers to select the best treatment for the patient and prioritize the right ADC for each patient. And with this, I think we can move on to another highlight of today.
Romualdo Barroso: Can I just add one thing that I think it’s really important to put in context is that the population included in DB-04 is different from the population from TROPiCS. So in TROPiCS, we have heavily pretreated patients in DB-04. We have patients that just received no more than one or two prior lines of chemotherapy and the use of prior CDK4/6 inhibitor was not mandatory, so they are less pretreated. We need to see the data to see the magnitude of benefit we are at now, that there is an improvement in PFS and OS, and we are all excited, but it’s important to mention that the populations are not exactly the same.
Paolo Tarantino: Absolutely. And so I think the second highlight of the day where CDK4/6 inhibitors, and there was an overall survival update of PALOMA, PALOMA-2, sorry, which was the first line trial of endocrine treatment with, or without palbociclib for hormone receptor-positive metastatic breast cancer, and that was kind of unexpected. These results were kind of unexpected given what we have seen with the different CDK4/6 inhibitors in terms of PFS. So I would like a comment about that from Romualdo.
Romualdo Barroso: Yes. I think it’s, well important, to stress out that the primary endpoint was PFS and regarding the primary endpoint for all these trials, they are very similar, they look similar. Now exploring the secondary endpoint and of course, overall survival is extremely important. The truth is that PALOMA-2 was not able to show an advantage in terms of overall survival. There are several hypotheses to explain this, but the fact is that differently from ribo and bema trials, we didn’t see a survival benefit in this population.
Paolo Tarantino: So yeah, it was interesting and expected to see this and of course there’s some speculation. Also, if the CDK4/6 inhibitors act in different ways, because they are different molecules, they have different side effects. We have seen that in the early setting, adjuvant abemaciclib was effective, whereas adjuvant palbociclib was not effective in two trials so some people are extrapolating. It’s very early and very hard to extrapolate, but still it’s a very complex matter and we are going to need to discuss this a lot to identify the best treatment strategy for the patient and in the same space of CDK4/6 inhibitors, it was a very intriguing study, which was the MAINTAIN randomized trial. It was a Phase II randomized study, randomizing patient that have already received endocrine treatment and CDK4/6 inhibitors to either continue CDK4/6 inhibitors by changing the endocrine partner or just receiving endocrine treatment.
Paolo Tarantino: Something that was really interesting is that in the study, the fulvestrant, or in general, the second line endocrine treatment, performed really poorly. This is something that we’re seeing in many trials. Also, the elacestrant trial showed that fulvestrant, in general, endocrine treatment, after progression to CDK4/6 inhibitors, performs poorly in monotherapy, but the ribociclib arm instead show the doubling of PFS and that was intriguing to me. What was your opinion, Romualdo?
Romualdo Barroso: Well, definitely it’s intriguing it’s promising the data. The only big issue that I think we need to highlight is that 87% of the population included in this trial received palbociclib. So I’m not sure whether we can extrapolate this data to patients that would receive ribo or abemaciclib. We don’t know this answer.
Paolo Tarantino: I agree. And then there were also some highlights on genomic analysis of SOLAR-1 with alpelisib, which also was interesting and the FACTION trial also an update with capivasertib. But since we have a short time, I would like to touch one last point, which is the BR002 trial, NRG-B002, which was a trial testing if it’s useful to ablate metastasis in oligometastatic breast cancer patient, and actually the study was negative. It showed that in patient that receive ablation either with stereotactic radiotherapy or with surgery of the metastasis, there was no benefit in the long term compared to patient not receiving any local treatment, but just systemic treatment. What was your opinion of this study?
Romualdo Barroso: Yeah, so the point of oligometastases and how to best treat these patients was also very expected, and unfortunately the trial didn’t show any superiority of offering local therapy for this patient. I think the major question here is outside a clinical trial systemic treatment as the only option for this patient.
Paolo Tarantino: Absolutely agree. Breast metastatic study breast cancer is a systemic disease. We know that the mainstay is always systemic treatment. I think one caveat of the study was that it was a small study, of course, and most of the patients were hormone receptor-positive and we know that triple negative and HER2-positive behave in a very different way. I think this trial leaves the open question, if it’s useful to do something locally for this patient, but for sure we have no strong data yet to propose loco-regional treatments, so it’s something personally I will just consider in selected cases, but just as adjunct as you say to the systemic treatment, which remains always the mainstay. I think with this, we covered the news from today, which was very exciting. It was such a terrific session and we are also so exciting waiting for tomorrow for DB-04. Hopefully in the future, we are going to be able also to discuss with those data and see better what’s coming for breast cancer.
Romualdo Barroso: Yeah, it’s definitely. The trial is very expected and the meeting was, this session was extremely interesting and thanks so much.
Dr Tarantino reports the following conflicts of interest: Consulting: AstraZeneca.
Dr Barroso reports the following conflicts of interest:
Receiving speaker bureau fees: AstraZeneca, Daichi-Sankyo, Eli Lilly, Pfizer, Novartis, Merck, and Roche. Consultant/advisor: AstraZeneca, Eli Lilly, Libbs, Roche, Merck. Support attending medical conferences: AstraZeneca, Roche, Eli Lilly, Daichi-Sankyo, and Merck.
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