Welcome to The Breastcancer.org Podcast, the podcast that brings you the latest information on breast cancer research, treatments, side effects, and survivorship issues through expert interviews, as well as personal stories from people affected by breast cancer. Here’s your host, Breastcancer.org senior editor Jamie DePolo.
Jamie DePolo: Hello, I'm podcasting from the 2022 San Antonio Breast Cancer Symposium. My guest is Dr. Nicholas Turner. Dr. Turner is a professor of molecular oncology at the Institute of Cancer Research in London, and a consultant medical oncologist at the Royal Marsden NHS Foundation Trust.
At this symposium, Dr. Turner presented research on experimental capivasertib in combination with Faslodex as a potential new treatment for advanced-stage, hormone receptor-positive, HER2-negative breast cancer that has stopped responding to an aromatase inhibitor.
Dr. Turner, welcome to the podcast.
Nicholas Turner: Thanks very much for having me.
Jamie DePolo: So, could you tell us what type of medicine capivasertib is and how it works?
Nicholas Turner: So, capivasertib is from the group of treatments that are called targeted therapies. What it does, is inhibit a protein called AKT. We know from lots of research that AKT is very important for the growth and survival of cancer cells of the most common form of breast cancer, that which is hormone receptor-positive, and HER2-negative.
Jamie DePolo: Okay, and could you briefly tell us about the CAPItello-291 trial that was looking at capivasertib in combination with Faslodex?
Nicholas Turner: The CAPItello-291 study was in women with advanced breast cancer, which is not curable but highly treatable, and what we need is new treatments that are going to help women live their lives longer and well. So, the CAPItello-291 study took women who had progressed on their first hormone therapy, where the standard of care is Faslodex, fulvestrant, that you mentioned earlier. And it took 708 women and randomized them between Faslodex and the new treatment capivasertib, or Faslodex and placebo alone.
Jamie DePolo: Okay, and what were the results? What did you find out?
Nicholas Turner: Well, the results were that capivasertib quite substantially improved how long fulvestrant worked for. So, overall, the treatment improved from 3.6 months, just on fulvestrant and placebo, to 7.2 months on capivasertib and Faslodex.
Now, the study actually had two objectives. One was to look overall. But we also looked at what was called AKT pathway-activated tumors. And these are tumors that have got mutations in them that activate AKT. And in this subset of patients, capivasertib looked like it was even more effective. In them on just on fulvestrant to placebo, there was 3.1 months, and this increased to 7.3 months on capivasertib and fulvestrant. So approximately, in both groups, doubling how long treatment was working for.
Jamie DePolo: Okay, and I want to ask, the AKT pathway, does that have anything to do with the tumors potentially becoming resistant to the first hormonal therapy treatment?
Nicholas Turner: Yeah. We've had a lot of research over the years that have shown that AKT activation is one of the main ways that tumors can become resistant to hormone therapies. And that's probably one of the main reasons that capivasertib has shown such substantial efficacy in the study. It's not only shutting down AKT, it's helping the hormone therapy fulvestrant to work.
Jamie DePolo: Okay. So, now we have CDK 4/6 inhibitors, too, that are the standard of care. So, can you put your results in context with that?
Nicholas Turner: Sixty-nine percent of people who went into our study had had a CDK 4/6 inhibitor before. So, how the sequence of treatment is looking, is when people unfortunately are diagnosed with advanced cancer, the standard of care now as a hormone therapy given with CDK 4/6 [inhibitors], and this study was looking at people whose cancer had unfortunately started growing again after their CDK 4/6 inhibitor. And why this study is so important, is it's the first really big study of a treatment like capivasertib to recruit after CDK 4/6 inhibitors became a standard of care. So, we're really getting contemporary information, just like people are treated nowadays, which gives us real confidence that the results we see will translate into the clinic, of people as they are now with their cancer.
Jamie DePolo: Okay. I'm also curious, too. So, CDK 4/6 inhibitor is standard of care. Is it possible, because of the way capivasertib works, that it would make a CDK 4/6 inhibitor more effective? Like the cancer would start responding to do that, again? Is that something you plan to look at?
Nicholas Turner: Absolutely. It's a great question. And actually, the very first stages of the clinical trial that will looked at are being initiated.
So, we know CDK 4/6 inhibitors have had a really transformative effect on women with advanced, hormone receptor-positive breast cancer, but unfortunately, most people eventually progress on them. So, how about we bring capivasertib that works really well in that second-line setting, and bring it into that first-line setting, and assess whether it could make CDK 4/6 inhibitors and first line-treatment even better? And that's a clinical trial that's been initiated from its early stages, it probably will be some years until we get the result, but I think it'll be a really interesting study for us to look out for the results for in the in the coming years.
Jamie DePolo: Sure. And I'm thinking from the patient perspective, too, a CDK 4/6 inhibitor as a pill is easier to take the going in for a Faslodex injection every so often. Just easier.
Nicholas Turner: That is true. Faslodex injections are given once a month. They're not the nicest injections to have. They can be pretty painful. They're given in the buttocks. But I mean, it is, other than that, a really well-tolerated treatment and actually, for some people, they find that easier than taking a pill every day.
Jamie DePolo: True. Okay. And then last question, if you could help me put some of the research from the whole symposium in context.
There were other presentations on other experimental medicines aimed at the same type of cancer: advanced-stage, hormone receptor-positive, HER2-negative that had grown while being treated with hormonal therapy. There was one on camizestrant, there was one on elacestrant. So where does capivasertib kind of fit into all that? As a patient, what do I think about all this?
Nicholas Turner: Yeah. I think it's such an exciting time to be involved in breast cancer research, because we've got these and many other really exciting new treatments coming forward. So, the other drugs you referred to, camizestrant and elacestrant, are a new type of hormone therapy called oral SERDs [selective estrogen receptor downregulator]. What they are really, is an oral form of the fulvestrant treatment that we talked about that is given by these injections. And the oral SERDs look like they can be better than fulvestrant. And so they're a better hormone therapy, capivasertib our AKT inhibitor, is a targeted therapy works completely differently. And so, these are exciting new ways of treating breast cancer, potentially in the future we'd like to see them both together. So, we'd like to see the oral SERDs combined with capivasertib, where potentially both are doing better together and if you combine them, they could do even better again, as that combination.
Jamie DePolo: Okay. Thank you so much for helping me understand all this. I appreciate your time.
Nicholas Turner: Thank you very much, Jamie.
Thank you for listening to The Breastcancer.org Podcast. Please subscribe on iTunes, or wherever you listen to podcasts. To share your thoughts about this or any episode, email us at podcast@breastcancer.org, or leave feedback on the podcast episode landing page on our website. And remember, you can find a lot more information about breast cancer at Breastcancer.org, and you can connect with thousands of people affected by breast cancer by joining our online community.
