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MA.17R Trial Data Results

Insights From:Ruth O’Regan, MD, University of Wisconsin;Hope S. Rugo, MD, UCSF
Published: Friday, Oct 28, 2016


Transcript:

Hope S. Rugo, MD: The MA.17R Trial is our most recent data which helps us understand the value of extending endocrine therapy. We previously had data from the aTTom and ATLAS Trials that looked at extending tamoxifen after 5 years out to 10 years, and showed an improvement actually in disease-free survival. But, the data was very complicated with some patients who weren’t randomized, some who didn’t take their therapy, and competing toxicities such as endometrial cancer in the older-aged population. Now that aromatase inhibitors are generally our first-line treatment in the adjuvant setting for postmenopausal women with hormone receptor–positive breast cancer, the question has arisen whether or not we could substitute aromatase inhibitors for extended duration.

Prior to MA.17R, all the data we had was from MA.17, which showed us that, if you took 4 to 6 years of tamoxifen and then continued on with 5 years of the aromatase inhibitor, letrozole, you significantly reduced the risk of recurrence, and also distant recurrence. And, this data was particularly important in women who had high-risk disease which, of course, fits nicely into our understanding of risk. So, women who had node-positive disease, or women who are premenopausal at diagnosis but postmenopausal at 5 years, benefitted more than the rest of the entire population in MA.17. After MA.17 was published, the interest was whether or not even longer duration of therapy would be useful.

MA.17R was originally designed to randomize women who had been on MA.17, taken 5 years of tamoxifen, 5 years of an AI, and then would be randomized to either placebo or an AI from year 10 to 15. It turned out there weren’t very many women, and they couldn’t really power the trial appropriately. So, they allowed patients to be randomized and enter on study, who had taken 5 years of an AI as up-front therapy. It’s a combined population of about 2000 women with early-stage hormone receptor–positive breast cancer. What they showed for the first time was that extending aromatase inhibitor therapy out to 10 years reduced the risk of recurrence and improved disease-free survival by an absolute amount of about 4%.

So, why is this information controversial? Why is it not something that we should be doing for all patients? Well, the issue really is not just disease-free survival. What we want to do by continuing therapy is to reduce the risk of distant recurrence. Because when you’re continuing treatment that has obvious side effects for longer, and longer, and longer, you may have an impact on quality of life. We’ll talk about that a little bit more. But, in addition, it’s just hard. It’s an issue for women in a number of different ways. When you’re looking at invasive recurrence, that difference was miniscule in MA.17R. The biggest difference was the risk of contralateral new breast cancers. That’s going to be a very individual decision for women, whether or not that’s worthwhile.

Now, what is likely the case is that, if you selected a group of women who still had a very high residual risk of distant recurrence after 5 years of an aromatase inhibitor, we would indeed see a benefit. So, MA.17R, which showed this improvement in disease-free survival, is data that needs to be taken with a great deal of caution and applied to individual patients who remain at extremely high risk of distant recurrence after 5 years of adjuvant aromatase inhibitor therapy. If a woman has taken 5 years of tamoxifen, and then 5 years of an AI, their risk, of course, will be slightly lower still than those women who were approaching that question at year 6 versus year 11. We need to take that into account when we’re making those decisions. I think that the big issue when you make decisions, as well, has to do with tolerance of therapy, and that’s a question for which there are some data that we can use in order to make decisions.


Transcript Edited for Clarity
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Transcript:

Hope S. Rugo, MD: The MA.17R Trial is our most recent data which helps us understand the value of extending endocrine therapy. We previously had data from the aTTom and ATLAS Trials that looked at extending tamoxifen after 5 years out to 10 years, and showed an improvement actually in disease-free survival. But, the data was very complicated with some patients who weren’t randomized, some who didn’t take their therapy, and competing toxicities such as endometrial cancer in the older-aged population. Now that aromatase inhibitors are generally our first-line treatment in the adjuvant setting for postmenopausal women with hormone receptor–positive breast cancer, the question has arisen whether or not we could substitute aromatase inhibitors for extended duration.

Prior to MA.17R, all the data we had was from MA.17, which showed us that, if you took 4 to 6 years of tamoxifen and then continued on with 5 years of the aromatase inhibitor, letrozole, you significantly reduced the risk of recurrence, and also distant recurrence. And, this data was particularly important in women who had high-risk disease which, of course, fits nicely into our understanding of risk. So, women who had node-positive disease, or women who are premenopausal at diagnosis but postmenopausal at 5 years, benefitted more than the rest of the entire population in MA.17. After MA.17 was published, the interest was whether or not even longer duration of therapy would be useful.

MA.17R was originally designed to randomize women who had been on MA.17, taken 5 years of tamoxifen, 5 years of an AI, and then would be randomized to either placebo or an AI from year 10 to 15. It turned out there weren’t very many women, and they couldn’t really power the trial appropriately. So, they allowed patients to be randomized and enter on study, who had taken 5 years of an AI as up-front therapy. It’s a combined population of about 2000 women with early-stage hormone receptor–positive breast cancer. What they showed for the first time was that extending aromatase inhibitor therapy out to 10 years reduced the risk of recurrence and improved disease-free survival by an absolute amount of about 4%.

So, why is this information controversial? Why is it not something that we should be doing for all patients? Well, the issue really is not just disease-free survival. What we want to do by continuing therapy is to reduce the risk of distant recurrence. Because when you’re continuing treatment that has obvious side effects for longer, and longer, and longer, you may have an impact on quality of life. We’ll talk about that a little bit more. But, in addition, it’s just hard. It’s an issue for women in a number of different ways. When you’re looking at invasive recurrence, that difference was miniscule in MA.17R. The biggest difference was the risk of contralateral new breast cancers. That’s going to be a very individual decision for women, whether or not that’s worthwhile.

Now, what is likely the case is that, if you selected a group of women who still had a very high residual risk of distant recurrence after 5 years of an aromatase inhibitor, we would indeed see a benefit. So, MA.17R, which showed this improvement in disease-free survival, is data that needs to be taken with a great deal of caution and applied to individual patients who remain at extremely high risk of distant recurrence after 5 years of adjuvant aromatase inhibitor therapy. If a woman has taken 5 years of tamoxifen, and then 5 years of an AI, their risk, of course, will be slightly lower still than those women who were approaching that question at year 6 versus year 11. We need to take that into account when we’re making those decisions. I think that the big issue when you make decisions, as well, has to do with tolerance of therapy, and that’s a question for which there are some data that we can use in order to make decisions.


Transcript Edited for Clarity
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