Breast cancer treatment updates from the 2020 ASCO Annual Meeting

The ASCO Annual Meeting is one of the largest cancer research events in the country. Researchers often first present the breast cancer studies that change our understanding of the disease and lead to new treatments at this annual event.

The scientific program for this year’s meeting was held virtually May 29 to 31. Despite the new format, the 2020 ASCO Annual Meeting was full of new studies and information that will guide treatment in years to come.

We’re here to help you understand the science and what it means for your care. LBBC’s executive vice president for strategy and mission, Catherine L. Ormerod, MSS, MLSP, spoke to Erika P. Hamilton, MD, about some of the most important breast cancer findings to come out of this year’s event. Dr. Hamilton is director of the breast cancer program at the Sarah Cannon Research Institute and presented the breast cancer highlights session at the 2020 ASCO Annual Meeting. Watch, listen, or read the transcript below.

Read reports from important studies and all of LBBC’s coverage from the 2020 ASCO Annual Meeting

Catherine L. Ormerod, MSS, NLSP
Executive Vice President, Strategy & Mission

Ms. Ormerod is responsible for overseeing the implementation of all direct service and partnership initiatives. This includes leading efforts that increase public awareness of LBBC’s mission, overseeing the development and implementation of educational programs and services for those affected by breast cancer, and helping to cultivate and develop LBBC’s relationships with new and existing partner companies. She has more than 20 years of experience in the nonprofit and academic sectors, especially in the areas of communications and program and organizational development. Read more.

 

Erika Hamilton, MD
Director, Breast and Gynecologic Cancer Program
Sarah Cannon Research Institute/Tennessee Oncology
Chief Executive Officer, Living Beyond Breast CancerDr. Hamilton is director of the breast cancer research program and gynecologic cancer research program at the Sarah Cannon Research Institute. She came to SCRI in 2013 as an investigator in drug development with a women’s cancer focus and was named director in 2015. She sees patients who have breast or gynecologic cancers in both the phase I drug development unit and the standard of care clinic including phase II/III clinical trials. Dr. Hamilton is a partner within Tennessee Oncology. She is board certified in both internal medicine and oncology. Read more. 

 

Cathy Ormerod (00:01):

Hi everybody, this is Cathy Ormerod. I'm the executive vice president for strategy and mission at Living Beyond Breast Cancer. At the end of every May, I enjoy attending the American Society of Clinical Oncology's annual meeting. We get to hear the latest research. We always go with lots of hope that patient outcomes will improve.

But of course, this year we could not go to Chicago. And the 42,500 who attended last year attended virtually, myself included and our guest. But the good news is there was some good news out of ASCO, and that's what we're here to talk about today. I'd like to thank our sponsor Genentech for providing us funds to present this video and present information to all our constituents.

I'd like to welcome Dr. Erika Hamilton, the director of breast and gynecological cancers at the Sarah Cannon Cancer Research Institute in Nashville, Tennessee. Dr. Hamilton actually gave the metastatic overview on the second day of ASCO for breast cancer. We'll be talking about some of the things she discussed there, but we'll also be talking about some of the early stage breast cancer research findings that were presented.

Welcome, Dr. Hamilton. How was your virtual ASCO? How was it presenting in front of the camera?

Erika P. Hamilton, MD (01:34):

It was different. I think there were some special challenges of how to carve out time for ASCO and do everything remotely. But I think it was really inspiring that despite everything that's going on with COVID that the meeting still ended up going across as well as it did and so much new research presented. I'm really grateful for that.

Cathy Ormerod (01:57):

Yeah. Well, thank you for doing this today. I first met you on Twitter and your Twitter handle is @ErikaHamilton9.

Let's get into it. What did you find most exciting at ASCO this year for breast cancer?

Erika P. Hamilton, MD (02:14):

Yeah, it depends on what genre. I was very inspired actually to see that the E2108 study was presented at the plenary of ASCO this year. It's what one would often call "a negative study" because the results were that intervention did not improve overall survival. But I think it was a really important study to answer an age-old debate about whether doing surgery and local treatment for de novo [metastatic] breast cancer improves outcomes.

I think what that stood for and what it meant to take a study that's negative, and say as a community, we feel that not only celebrating a great drug is exciting, but also answering these debates about how we best treat people to improve their outcomes was really great as well.

Cathy Ormerod (03:06):

Yeah. Why is that important though? Surgery and radiation for metastatic de novo patients, why does that seem important to them and why is it a question that needed to be answered?

Erika P. Hamilton, MD (03:18):

Yeah, it's been a debate for a long time. We've had studies that have been on both sides of the fence. The majority of previous studies have been what we call retrospective reviews. We essentially look back and we take a population of patients that went to surgery and we take a population of patients that didn't, and we say, who did better?

A lot of those come out with the patients that go to surgery do better, but that introduces so many different types of bias. We tend to take younger people to surgery. We tend to take people that are doing better on their treatment, maybe have fewer sites of disease, those that have a really great performance status. So that's not really the way a trial like this should be designed.

Dr. Khan in E2108 designed the trial where people that had stable disease or disease control for 4 to 8 months on systemic therapy were actually randomized either to go to surgery or not. This was just a very clean design trial, and it showed that there was no improvement in overall survival for doing surgery in those with de novo breast cancer.

In the U.S. about 6 percent of patients are de novo metastatic disease, so this isn't an incredibly rare question. It's one that comes up in our clinics quite frequently.

Cathy Ormerod (04:36):

And it's related to quality of life, right? And patients are so interested in improving their quality of life.

Erika P. Hamilton, MD (04:42):

It is, it's related to a lot. Obviously outcomes and survival was very important and that's what ended up being negative. But it does have to do with quality of life, having surgery, if it's not going to get you anything is probably not something a whole lot of people would sign up for.

But the other question is that I hear this almost being misinterpreted now, that we should never take anybody to surgery. And that's not the case either. For somebody that has a locally advanced breast cancer that's causing them pain or problems that's certainly still on the table. Now we know that doing that's probably not going to affect survival. It's more of a palliative thing we do for symptomatic relief.

Cathy Ormerod (05:26):

And then other big news of course, was the HER2CLIMB news, tucatinib (Tukysa). Can you tell us more about that?

Erika P. Hamilton, MD (05:34):

I'll disclose that I was one of the investigators on the HER2CLIMB study. So yes, this is the tucatinib, which is a novel oral tyrosine kinase inhibitor, but unlike neratinib and lapatanib, tucatinib only inhibits HER2 and not EGFR. A lot of our side effects from these tyrosine kinase inhibitors come from EGFR being inhibited, the rash and the diarrhea.

We had already seen the results, tucatinib had already had approval, but at ASCO, it was updated that subset of patients that had brain metastasis and improved progression-free survival and overall survival for patients with both all-comer brain metastases, so stable and treated, untreated asymptomatic, or treated and subsequently progressive, and also the subset of 60 percent of the brain mets on study that were active. I think this is just really good data that we're influencing outcomes for these women and it's a great drug.

Cathy Ormerod (06:37):

Great drug. I know patient advocates were thrilled with the study design, including people with brain mets, and have been celebrating that design and hoping other researchers take note of that. And also men were included. I think there were only five, is that right?

Erika P. Hamilton, MD (06:58):

Yeah. They were included. There weren't a lot of men, but I think the inclusion of brain mets is incredibly important.

Cathy Ormerod (07:06):

Yeah. People are very, very excited about that. Keynote-355 for people with triple-negative metastatic breast cancer also got some attention. Can you tell us more about that one?

Erika P. Hamilton, MD (07:19):

Yeah. This is a trial that was not designed unlike IMpassion130, which is our atezolizumab approval in first-line metastatic triple-negative breast cancer, but this was pembrolizumab and it was added to standard first-line treatment for triple-negative breast cancer, including all comers. Instead of looking at PD-L1 score by IHC, they looked at this combined positive score. A different assay, but we saw pretty similar results in the fact that it was that high score, a combined positive score of at least 10, where people statistically did better with progression free survival.

We haven't seen any overall survival from Keynote-355, so I'm very excited to see that, but as you all know, there's a little bit of controversy about the overall survival and IMpassion as well, because the way they designed their hierarchical analysis, we were only supposed to test in certain populations if the initial population was positive. And so there's a little bit of statistical argument of whether that analysis was really valid in IMpassion, but I think certainly encouraging and practice confirming that there is a population of high PD-L1 expression in the first line setting where patients benefit from this drug.

Cathy Ormerod (08:35):

The role of testing is increasing every year. You researchers are targeting more and more specific areas. What is the difference in the testing that you talked about?

Erika P. Hamilton, MD (08:52):

Yeah, it's different assays, so they're scored differently. It's just the way we look at PD-L1 and how we combine the score. There's a variety of different ways out there. I don't think with atezolizumab they looked at some other ways to do it, not the SP142, but 22C3 and they all have some differences.

I think probably what's important is that we use the assay where the drug is approved. For atezolizumab it's probably SP142, for pembrolizumab, we'll see what ends up happening with that drug. But again, we were able to predict the population that benefited with the combined positive score.

It becomes increasingly confusing. It's also interesting with the SP142 assay, it's different than the way we test for PD-L1 for lung cancer. Just some unique spots where we have to be a little bit careful with what tumor type we're looking at.

Cathy Ormerod (09:52):

Thank you. Thanks for clarifying that. In early-stage breast cancer, Dr. Angie DeMichele, who's on our medical advisory board and a good friend, reported on the early-stage progress that's been made. There was a lot of talk about escalation and de-escalation of treatment, particularly for HER2-positive breast cancers. Can you explain a little bit about that?

Erika P. Hamilton, MD (10:15):

Yeah, I'll be honest, I don't love the words escalation and de-escalation. We use them very frequently in the medical community and it means something to me, but I think it can be confusing for the lay person where you hear it, well, I don't want to get less therapy, right? I don't want to be de-escalated.

I think it's important just to clarify that what de-escalation and escalation means is just giving the right size treatment for the individual patient. It's tailoring the treatment and what the individual patient needs.

We don't want to over-treat people, we also don't want to under treat people. It's just getting that balance right. It's not unlike the KATHERINE data, right. KATHERINE was our adjuvant TDM1 [ado-trastuzumab emtansine] study, and it was the biggest win we've really had in HER2-positive breast cancer and quite some time and improvement in disease-free survival of about 13 percent.

I think the reason that trial was so successful is because we accurately captured a group of patients that were very high risk and they were high risk based on the fact that they did not have a pathologic complete response, meaning their tumor had not completely melted away when they went to surgery. And then by adding the extra drug TDM1 we improved things by 13 percent, [from] 77 all the way up into the high 80s. This was quite impressive.

So, I just want to clarify that escalation and de-escalation is just tailoring therapy for individual risk scenarios.

Cathy Ormerod (11:44):

The PHERGain study, can you speak to that?

Erika P. Hamilton (11:47):

PHERGain was a very complicated study. Essentially what they did is they used antibody HER2 treatment and dropped the chemotherapy out for some patients, and other patients got chemotherapy with HER2 treatment. And then they did a PET scan that was tagged and based on how the tumor was reacting to that treatment, they either continued with the antibodies alone, or, if the tumor wasn't responding the way they wanted to, they switched over to chemotherapy.

Cathy Ormerod (12:20):

And so it was really asking the question of, based on some functional imaging of people's tumor, can we predict a lower subset of patients that may do just as well with less toxic treatment? Less toxic, it's the key here I think, maybe rather than de-escalation or escalation, getting the right treatment at the right time.

Also related to that is the MINDACT study, which is all about predicting, who needs chemotherapy and who doesn't. This was actually an update, I think, of an ongoing study. Could you tell us about that?

Erika P. Hamilton, MD (12:56):

Yeah, it was. MINDACT was a long-term follow up and the MINDACT trial has to do with the Mammaprint assay. The Mammaprint assay is a genomic assay where we send a small piece of tumor off to a lab that tells us genomically and from a DNA and gene perspective, how likely is this tumor to come back?

We have well-known things, you'll hear in this trial: clinical, either low or high, and genomic, low or high. Clinical high means size of the tumor and nodal status and these types of things. What we found is in the clinical high, but genomic low, so the Mammaprint assay suggested that this was a low risk tumor to come back, that people did incredibly well long term, so no benefit of chemotherapy there,.

We already know if you're a clinical low and genomic low, no chemo. And if your clinical high and genomic high, you need chemo. This trial was really looking at that intermediate zone where your clinical and your genomic doesn't match and what to do there.

I think it’s incredibly reassuring that we've now identified another population that clinically may look like they're high risk [for cancer] to come back. But with this assay, we can re-categorize them into the low-risk bucket and save them from having to do chemotherapy,

Cathy Ormerod (14:19):

Which is good news, indeed. Moving on to triple-negative breast cancer in the early stage, there was a study with Xeloda [capecitabine] and with people who still had some cancer after a surgery. Could you comment on that?

Erika P. Hamilton, MD (14:37):

Yeah. This was a metronomic capecitabine study. Metronomic chemo is traditionally very low dose chemo, less than we give. This study gave patients 1 year of metronomic capecitabine, so very low dose capecitabine and showed that cancers were much less likely to come back with that capecitabine.

This is very similar to CREATE-X, which was another trial where we used regular-dose capecitabine for six to eight cycles. And again, showed that same improvement in diseas- free survival, or converting more people into potential cure.

I think the tricky thing about capecitabine always for me is that a lot of these studies are done in Asia and Asian women, for some reason, seem to tolerate and be able to tolerate higher doses of capecitabine than a lot of Caucasian Western women here tend to be able to tolerate.

I don't know, without seeing overall survival and final data, whether I would switch to metronomic capecitabine over the CREATE-X traditional regimen right now. But I think it's reassuring for those women that may not tolerate standard doses from the CREATE-X trial that at least we have this to fall back on.

I think it's also very interesting the six to eight cycles versus a year. I'd love to see which one actually ends up being better tolerated, a higher dose for a shorter time or a lower dose for longer, but we don't have all of that data.

Cathy Ormerod (16:11):

In triple negative there seemed to be some more news. What is your take on the big picture for triple negative?

Erika P. Hamilton, MD (16:19):

Yeah, one of the other things that I was excited about was more broadening of who may benefit from PARP inhibitors.

There were two abstracts presented, one showed clear in a way that people with PALB2 mutations, which honestly is a relatively new mutation we've just learned about in the past several years, benefit incredibly from the PARP inhibitor.

I think that puts another small population into the bucket that we may use it. In general, I think we're just getting smarter at realizing that all triple negatives are not the same and to try to classify these into buckets, whether that's the PD-L1 positive bucket, whether this is hormone homologous recombination deficiency that may benefit from a PARP inhibitor. But trying to break these up into more little buckets and treat them individually.

Cathy Ormerod (17:13):

Of course the topic on everyone's mind getting treatment during the time of COVID. There were some announcements made at ASCO and could you just summarize some key takeaways from that?

Erika P. Hamilton, MD (17:27):

Yeah, it's really tough. I think it's really hard to come up with any type of consensus statement that's a one size fits all approach and that's because COVID is affecting different cities, and different communities, different like all across the world. And each person's individual risk may be very different.

Somebody that's on an adjuvant aromatase inhibitor, I don't think we probably think they're at much higher risk if they were to contract COVID to have a poor outcome. Then what we've seen, some lung cancer patients, maybe patients on immunotherapy, patients that have low counts because of chemotherapy, we're more worried about that.

I think it's an individual conversation that each patient needs to have with their physician about what's happening in their community, what their individual risk may be, what other medical conditions they have that put them at more or less risk of that and make some decisions accordingly.

I think we're all trying to at least be very cognizant of making people neutropenic right now with COVID. And so that may be picking a chemotherapy next that for metastatic patients that doesn't have as much count abnormalities and low counts to some other chemotherapies. I think that's liberally using GCSF or growth factors to make sure that white counts don't drop. But really, it's a quite complicated decision that has to be assessed on a case by case basis to be quite honest.

Cathy Ormerod (18:51):

Great. Well, that's great takeaway information.

Dr. Hamilton, thank you so much for bringing us the news from ASCO 2020, even though we weren't there. I'm glad to say the research is going on and good things are happening for patients.

Erika P. Hamilton, MD (19:07):

Yes, absolutely. I think one of the best things about ASCO being virtual is that more people got to join and got to see the research. There's a variety of people that can't or aren't in a position to travel. I think maybe even more advocates were able to log on and participate in ASCO this year, and I think that's a huge plus.

Cathy Ormerod (19:26):

Yes, a big thank you to ASCO for making registration free for patient advocates. That was a big plus, thank you so much.

For everyone out there, we have lots more content on ASCO on LBBC.ORG. And if you need support, we also have our Breast Cancer Helpline, and we have some closed Facebook communities. Thanks again to Dr. Hamilton and we'll see you again soon I hope, in person.

Erika P. Hamilton, MD (19:58):

Thank you so much for having me, appreciate it.