Breast Cancer Research Highlights — Heard in the Halls: ESMO 2019

Anne White: This is Anne White, president of Lilly Oncology here at ESMO 2019. 

Jamie DePolo: Anne, would you like to talk about some of the research that’s been presented focusing on breast cancer? 

Anne White: Yes, it’s been an incredibly exciting ESMO for breast cancer with a lot of new advances. Lilly here is sharing a couple of new data releases that I think are particularly exciting to the breast cancer population for breast cancer patients, particularly, and that is this afternoon, we’ll be sharing the overall survival results for our MONARCH 2 study. So, this was a study of Verzenio in combination with fulvestrant, and so it’s an incredibly important population and many, many women receive fulvestrant as part of their treatment. 

And so we’re going to be sharing the fact that we now have a survival benefit for those women, that women will live longer when treated with Verzenio as the result of the data that we’ll be sharing on this study. It’s actually about nine-and-a-half months longer than the fulvestrant arm. 

So, the reason that we’re so excited about that is we’ve heard from breast cancer patients repeatedly that survival is the most important outcome for them. The fact is they want to live longer to be with their families, to see their kids graduate from high school, to see their first grandchild get born. And so that’s where survival matters, because survival is really the gold standard of cancer care is that you get to live longer and live a high-quality life, enjoying the moments that matter and just having more moments with your family. 

So, when we saw that data, when we saw that we were able to actually extend survival, we were just thrilled. And I think that’s really what motivates our cancer researchers is that kind of really important outcome that makes such a difference in people’s lives. 

Jamie DePolo: And I’m going to ask you to explain just a little bit. This data was overall survival, because Verzenio was approved based on progression-free survival. So, not everybody understands the differences between those two. So, if you wouldn’t mind talking just a little bit about that? 

Anne White: Yes. Yes. That is correct in that Verzenio was originally approved based on progression-free survival as the other CDK4/6s were, and so this is really a measure of the time to a patient when they progress and then have to move onto another treatment. So their cancer has progressed to the point that the doctor has decided to treat them with something else. 

But survival, essentially, is a longer-term outcome. Patients in this study may have received other treatments after Verzenio, but then we measure the entire time that they’ve lived until, unfortunately, that they’ve passed away. 

And I think what’s so neat about this study is the fact that because breast cancer patients do have good treatments even after CDK4/6s, but yet we still are able to demonstrate a survival benefit, we really feel that this means that we have a robust result. Because it’s hard to show survival benefit when patients have gotten other treatments. That can complicate the results, it can sometimes make studies not significant. But the fact that we were able to demonstrate significance, I think, really reinforces that Verzenio itself adds a benefit. And so that’s why we were so excited. 

Jamie DePolo: Great. Now were there any other highlights in breast cancer research here that you noted? 

Anne White: Yes. So, another one that we were able to share from Lilly was the results, a HER2-positive population. So, this is an area that, unfortunately, there haven’t been as many advances for women, and so we were able to share the data yesterday in the first randomized controlled trial of abemaciclib, or Verzenio, adding benefit to those patients. So, we had nearly a 3 times improvement in their response rate for that trial. 

So, it shows that it truly is an option versus chemotherapy because the trial was basically versus chemotherapy, abema[ciclib], and fulvestrant plus trastuzumab versus trastuzumab and chemotherapy. And what we’ve heard from women repeatedly is they really like to delay the time to chemotherapy as much as possible. That’s obviously a different set of quality of life challenges that you face. 

And so I think the clinicians on our team were most excited because they got to see that result and said this is just another opportunity to help delay that time to chemotherapy and give women a high quality of life while they’re taking this medicine. 

So, good results on progression-free survival and really fantastic results on response rates, so we’ll continue to follow those patients for survival. That outcome will come later. But again, the first of these major trials to read out in HER2-positive, so we’re very excited about what’s next for them. 

Jamie DePolo: Great. Anything else that really stood out to you? 

Anne White: Well, there’s another one that I think is a first in the CDK4/6 class, which is we also had, in a predominantly Chinese population, we had a phase 3 readout that was highly significant in terms of progression-free survival and response rate in the Chinese population. So, this was the basis for a submission that we’ll be putting in for China to support a registration for women with metastatic breast cancer in China. 

And so, the first study done in an almost entirely Chinese population, really to make sure that we saw a robust response in that group. And so that was also exciting to see with very strong hazard ratios, which indicate the strength of the response was very good. 

So, again, a lot of great answers for women with breast cancer, and we’ll see even other molecules reading out at this meeting furthering the field. And so, you know, it’s really an exciting time when you look at the advances that we continue to make in translating science into solutions for patients. And that’s really the theme, I think, here at ESMO, is to take that breaking science, but then make sure it actually turns into results the patients can interpret and their physicians can use to make treatment decisions. I think there’s been a number of those at this meeting, so it is exciting. 

Jamie DePolo: The FDA recently asked all the companies who make CDK4/6 inhibitors to update the labeling about lung inflammation. And we got a lot of questions on our website, “Oh, what does this mean? I’m kind of scared. Does this mean I’m going to get pneumonia or something horrible?” And from the researchers I’ve talked to, it sounds like it’s very rare, but if you could talk to that? 

Anne White: One thing we do constantly following the launch of drugs is follow them to ensure that we’re understanding any safety signals that we see, and we and other manufacturers do this on all our products. And so as we’ve been launching the product, we and other CDK4/6 manufacturers have noticed some incidents, just very few, of interstitial lung disease, or pneumonitis, and so we’ve been tracking these closely. Again the incidence is very rare, but importantly, it’s an adverse event that if identified early can really be managed very carefully and thoughtfully and not turn into a significant issue for the patients. 

So, even though it’s rare, what we and the other CDK4/6 manufacturers agree with the FDA is that we would update our labels to make sure that physicians were really well informed that this rare event could happen. And most importantly, so that they watch for any early signs and signals that patients are having any difficulty breathing or concerns of that nature. Then they should mention that to their physician immediately, get screened, and make sure that that doesn’t turn into something more serious because this is something, that if well informed, physicians can make sure it does not turn into a challenging situation. 

So that’s why we were enthusiastic to support making sure that we got the word out that this can happen in a small number of patients. And so the FDA updated all of the labels on this just recently, which is a good move because then we make sure that patients are well informed. They should certainly ask their doctor if they have any concerns. 

One of the things that I think is exciting about the MONARCH 2 data, so this is Verzenio in combination with fulvestrant, is the results that we’ve seen in patients that have a poor prognosis. So, one such group of patients are those that, following surgery, they’re being treated with an endocrine therapy, but they’ve had a relapse or they progressed. And there’s another group of patients who are diagnosed with metastatic breast cancer, treated with an aromatase inhibitor, for example, but then also they progressed. So these are patients that have more aggressive disease overall. 

And what we saw in MONARCH 2 was a very robust response in these patients with a survival benefit for them that was, again, with a very positive hazard ratio, a very positive response rate, and progression-free survival, but importantly, again, that overall survival benefit. They lived longer compared to the patients on fulvestrant alone. And this is a group of patients that I just find it very motivating to offer answers to because there haven’t been other CDK4/6 inhibitors that have been able to offer that kind of response and survival benefit in those patients who are likely to do worse. 

A similar group that Verzenio has also demonstrated survival benefits now in this study were patients that have visceral disease. So, patients where that cancer has metastasized to the liver or other places in the body. And so again, we saw a really robust survival benefit compared to fulvestrant in those patients as well. 

And these were all predefined subgroups that we were looking at. So, you have to define which areas you’re going to look at before you start a study to make sure that that result is really robust, and so those were all predefined. 

And probably the one that motivates me as much is the delay to chemotherapy. Because having had family members with breast cancer and seeing them go through chemotherapy, it really does change your quality of life, and what you can do, and the freedom that you have to be with your family. And so we had a median time delay to chemotherapy on the Verzenio arm of 50 months, 5-0 months, until patients needed to move onto chemotherapy. 

And that to me… I have to say I got chills when I saw that result because I thought how wonderful it is to have that kind of quality time with your family. When every moment matters to have a high-quality moment where you can attend your family events and be with your kids and your husband, your partner. And so I just thought it was really meaningful, and my prediction is that breast cancer patients will find that pretty meaningful as well. 

Jamie DePolo: I’m sure they will, and that was for overall, that wasn’t just in those two specific populations you were talking about. 

Anne White: Right, that result was overall, that delay to chemotherapy was in the overall population. 

This podcast is made possible by the generous support of Lilly Oncology.