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Jamie DePolo: Hello, everyone, and welcome to the Breastcancer.org podcast. I’m Jamie DePolo, senior editor of Breastcancer.org. We’re on location at the 2017 San Antonio Breast Cancer Symposium. My guest is Dr. Debu Tripathy, professor of medicine and chair of the department of breast medical oncology at the University of Texas, MD Anderson Cancer Center.
Dr. Tripathy presented research on using Kisqali to treat pre-menopausal and peri-menopausal women with advanced-stage or metastatic hormone receptor-positive, HER2-negative breast cancer in conjunction with temporary ovarian suppression and tamoxifen or an aromatase inhibitor. And this was in the MONALEESA-7 study. Dr. Tripathy, welcome to the podcast.
Debu Tripathy: Thank you, Jamie.
Jamie DePolo: So tell me, why is this study important? Why did you think that using Kisqali to treat pre-menopausal or peri-menopausal women would be important?
Debu Tripathy: Well first of all, a significant number of patients with metastatic breast cancer are, in fact, pre-menopausal, and that number may be slightly going up over time. In this country, it’s estimated that about 20% of patients are pre-menopausal and in other parts of the world it’s even more. This is the first trial that was actually dedicated to women who were pre-menopausal. And the biology is different, the presence of estrogen creates for a different tumor environment.
We’ve known for many years that patients who are younger do have more aggressive breast cancer and the drugs that we use may work differently, so it was very important to design a study dedicated exclusively to this patient population so we could have the statistical power to make conclusive statements. In addition, tamoxifen, which is commonly used in pre-menopausal patients, has not been tested in combination with any of the CDK4/6 inhibitors like Kisqali or Ibrance. So, this was the first trial to compare those drugs as well in combination.
Jamie DePolo: Okay, that brings up a couple questions for me. One, I know in your study ovarian suppression was used, and I’m assuming that’s because there was an aromatase inhibitor involved. If a woman were being treated with tamoxifen and Kisqali, do you still need the ovarian suppression?
Debu Tripathy: At the current time you do. This study was designed for everybody to have ovarian suppression, including the patients on tamoxifen. And there was a study done about 17 or 18 years ago that actually looked at either tamoxifen or ovarian suppression or a combination of the two, and it turns out that a combination of the two was most effective. So it is generally assumed that no matter what drug you use, even tamoxifen, which is used in pre-menopausal patients, that ovarian suppression does add to the benefit.
Jamie DePolo: Okay, I see. Now was, in your study, was Kisqali used as a first treatment for the metastatic disease, or was it after the cancer had progressed while being treated with something else?
Debu Tripathy: It was used as first treatment. In this study, patients could not have received prior endocrine, or hormonal, therapy for advanced breast cancer. They could have used it for early-stage in the past. It did allow one cycle of chemotherapy. Sometimes patients are treated with chemotherapy first, and it was only a minority of patients in this study, but up to one chemotherapy for advanced breast cancer was allowed. But no hormonal therapy.
Jamie DePolo: Okay. And now your study, the results seem very good. The progression-free survival was longer. And I know, it sounds like you need more follow up to determine whether overall survival will be improved?
Debu Tripathy: That’s correct. Progression-free survival was nearly doubled, and so that was a very favorable result. There’s no difference in survival at this point, but very few patients, fortunately, have expired due to their disease. And this is true for all of the CDK4/6 inhibitors. In fact, the trials were designed really to pick up a difference in progression-free survival, because otherwise they would have to have been much longer. But you do bring up an important point, and that is, should we be demanding that all new approved drugs actually improve overall survival? And that’s a difficult question to answer.
What we did do in this study, though, is we looked at quality of life. Because over time, quality of life may fall as the cancer progresses, and we wanted to see if Kisqali made an impact on that. And that beta will also be presented. And in fact it did. If you look at patient-related outcomes based on questionnaires looking at physical functioning and side effects, quality of life, they actually were better in the Kisqali arm as well.
Jamie DePolo: Okay, and you bring up an important point, too, about side effects. Sometimes the side effects can be so severe that a woman may question, do I want to stay on this treatment. What were the side effects? Any different in the pre-menopausal women as opposed to the other studies looking at post-menopausal women?
Debu Tripathy: The side effect profile was pretty much in the same range. A lot of the side effects were actually due to side effects we typically attribute to aromatase inhibitors, and about 3/4 of the patients were on aromatase inhibitors and 1/4 were on tamoxifen. That was actually up to the patient and physician, unless they had recently had one or the other drug in the early-stage setting. If it had been less than a year, then they had to go on the alternate drug.
So a lot of the side effects were due to that. The one main side effect we saw due to Kisqali was a drop in the white count. It was usually asymptomatic. In fact, the development of an infection was quite rare; it was 2% or less. So the side effect profile was very similar as to what has been recorded with other drugs of this class.
Jamie DePolo: Okay. And help me understand, too, for this particular combination, would a woman stay on it as long as it is effective, or is it for a certain timeframe, like you get it for a year, you get it for 6 months?
Debu Tripathy: So the treatment duration is the same as we would normally use in practice for any cancer agent: as long as there is no progression of the cancer and the drug is being tolerated reasonably well, we continued on treatment, so that’s how the trial was designed.
Jamie DePolo: Okay, and finally, now, this is one study with favorable results. Do you think it’s possible that this particular study could change practice? I know Kisqali is already approved, so I guess potentially if a doctor thought that this might help a patient, the doctor could prescribe it in this way. Do you see practice changing, I guess, as a result of your study?
Debu Tripathy: Yes, primarily in pre-menopausal patients. I think in post-menopausal patients these drugs, CDK inhibitors in general, are very commonly used. In pre-menopausal patients, there was some hint that it may be effective. The earlier trials with Ibrance and Faslodex, some of those patients actually did receive ovarian suppression met with monthly injections, but it was a small subset of the study. It didn’t have the statistical power that this one had. So I guess what I would say is that physicians and patients can feel more confident now that if they are pre-menopausal, that this is clearly an effective therapy.
Jamie DePolo: Great. Thank you so much for your time. I appreciate it.
Debu Tripathy: Thank you for having me.
