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QOL Analysis of MA.17R and Treatment Decisions

Insights From:Ruth O’Regan, MD, University of Wisconsin;Hope S. Rugo, MD, UCSF
Published: Friday, Nov 11, 2016


Transcript:

Hope S. Rugo, MD:
Quality of life was assessed in the MA.17R population. That’s really important because when we’re making these decisions for the global population who have a small expected benefit in terms of risk of distant recurrence, we always need to think about risk versus benefit. Interestingly, the quality of life instrument in MA.17R did not show a deterioration of quality of life in the treatment arm versus the placebo arm, so the patients receiving continued therapy with letrozole. But, how does that really fit into what we see in our clinical population? What they saw were more menopausal-like symptoms, the exact same symptoms we’re used to seeing with aromatase inhibitors—more joint symptoms, but it didn’t cause deterioration. What could that reason be? Well, it turns out that women who tolerate aromatase inhibitors tolerate aromatase inhibitors. They’re not going to have more side effects than they already had. And, of course, we started with the baseline quality of life that they had while taking an aromatase inhibitor when they were randomized to placebo or not. So, it’s quite intriguing. Again, the self-selection may play a very big role. The selection of patients who tolerate therapy is really important because those patients will continue to tolerate therapy, and they won’t have ongoing symptoms which affect quality of life.

Ruth O’Regan, MD: The MA.17R study not only collected toxicity evaluations, but they also did do a quality of life analysis. And, overall, in the quality of life analysis, there wasn’t really a huge difference between the two arms. Certainly, there was some mild drop in quality of life in the patients who got the letrozole versus not, but it really wasn’t anything of much significance. However, they did notice an increased fracture rate with letrozole, an increased rate of new onset osteoporosis despite about 50% of patients were taking bisphosphonates, so that’s obviously a quality of life issue for patients. We don’t want them getting fractures. I think what we have to remember from the MA.17R study is that this is a highly selected group of patients because they’d already had 5 years of an aromatase inhibitor and had done fine with it. I think, most times, if we see joint pain, it occurs fairly early on in patients taking these drugs, so it would be pretty unlikely that after 5 years, a patient would suddenly get joint pain. I think they are very selected, and certainly in our practices, we see a lot of patients that just can’t do the 5 years or they don’t want to do more than 5 years of treatment because the joint pain, the menopausal symptoms are affecting their quality of life. So, I think with the caveat that this was a selected group of patients, there didn’t appear to be a huge difference in quality of life between the two arms.

Hope S. Rugo, MD: There’s always a risk for overtreatment in anything we do; treating women with early-stage breast cancer, whether it’s chemotherapy or hormone therapy. We now have to be, with these emerging data, more concerned about overtreatment with hormone therapy. I think in the past, it was all about undertreatment. Now, we don’t want to be treating everybody with 10 years of hormone therapy. Women who have a low risk of recurrence when they start still have a low risk at 5 years in terms of their ongoing risk of recurrence. So, I wouldn’t treat those women with extended adjuvant therapy. Once we get to node-positive tumors, larger T size, those are women whom I consider for extending adjuvant hormone therapy, particularly those women who are tolerating therapy well.

Ruth O’Regan, MD: As far as extending aromatase inhibitors to 10 years, I think we don’t really, at this time point, have a really good way of saying which patients need that approach versus not. I think, overall, if I have a patient who is at high risk of recurrence based on stage and nodal status, I do tend to keep those patients on aromatase inhibitors until at least 10 years, and some patients will even continue longer than that. I think what we really need is some molecular profile to tell us the biology of the cancer and indicate what the risk of having a recurrence beyond 5 years or beyond 10 years is, so that we can pick or select patients, in a more definitive way, who are really going to benefit from this treatment. So, I think we do it on an individual patient basis. I think it depends on what you think their risk of recurrence is beyond 5 years, but also how they’re tolerating the drug is very important.

Hope S. Rugo, MD: We’re waiting with bated breath for the results of the NSABP B-42 trial. It’s a cleaner study than MA.17R and likely will, in general, have probably randomized more women at higher risk. I don’t know the demographics of that trial yet, and I’m really waiting with a lot of interest in those results. I think that they’re going to help us a lot in understanding the benefit of extending AI therapy after 5 years in a more homogenous population and understanding the risks, as well as which patients are more likely to benefit.

Transcript Edited for Clarity
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Transcript:

Hope S. Rugo, MD:
Quality of life was assessed in the MA.17R population. That’s really important because when we’re making these decisions for the global population who have a small expected benefit in terms of risk of distant recurrence, we always need to think about risk versus benefit. Interestingly, the quality of life instrument in MA.17R did not show a deterioration of quality of life in the treatment arm versus the placebo arm, so the patients receiving continued therapy with letrozole. But, how does that really fit into what we see in our clinical population? What they saw were more menopausal-like symptoms, the exact same symptoms we’re used to seeing with aromatase inhibitors—more joint symptoms, but it didn’t cause deterioration. What could that reason be? Well, it turns out that women who tolerate aromatase inhibitors tolerate aromatase inhibitors. They’re not going to have more side effects than they already had. And, of course, we started with the baseline quality of life that they had while taking an aromatase inhibitor when they were randomized to placebo or not. So, it’s quite intriguing. Again, the self-selection may play a very big role. The selection of patients who tolerate therapy is really important because those patients will continue to tolerate therapy, and they won’t have ongoing symptoms which affect quality of life.

Ruth O’Regan, MD: The MA.17R study not only collected toxicity evaluations, but they also did do a quality of life analysis. And, overall, in the quality of life analysis, there wasn’t really a huge difference between the two arms. Certainly, there was some mild drop in quality of life in the patients who got the letrozole versus not, but it really wasn’t anything of much significance. However, they did notice an increased fracture rate with letrozole, an increased rate of new onset osteoporosis despite about 50% of patients were taking bisphosphonates, so that’s obviously a quality of life issue for patients. We don’t want them getting fractures. I think what we have to remember from the MA.17R study is that this is a highly selected group of patients because they’d already had 5 years of an aromatase inhibitor and had done fine with it. I think, most times, if we see joint pain, it occurs fairly early on in patients taking these drugs, so it would be pretty unlikely that after 5 years, a patient would suddenly get joint pain. I think they are very selected, and certainly in our practices, we see a lot of patients that just can’t do the 5 years or they don’t want to do more than 5 years of treatment because the joint pain, the menopausal symptoms are affecting their quality of life. So, I think with the caveat that this was a selected group of patients, there didn’t appear to be a huge difference in quality of life between the two arms.

Hope S. Rugo, MD: There’s always a risk for overtreatment in anything we do; treating women with early-stage breast cancer, whether it’s chemotherapy or hormone therapy. We now have to be, with these emerging data, more concerned about overtreatment with hormone therapy. I think in the past, it was all about undertreatment. Now, we don’t want to be treating everybody with 10 years of hormone therapy. Women who have a low risk of recurrence when they start still have a low risk at 5 years in terms of their ongoing risk of recurrence. So, I wouldn’t treat those women with extended adjuvant therapy. Once we get to node-positive tumors, larger T size, those are women whom I consider for extending adjuvant hormone therapy, particularly those women who are tolerating therapy well.

Ruth O’Regan, MD: As far as extending aromatase inhibitors to 10 years, I think we don’t really, at this time point, have a really good way of saying which patients need that approach versus not. I think, overall, if I have a patient who is at high risk of recurrence based on stage and nodal status, I do tend to keep those patients on aromatase inhibitors until at least 10 years, and some patients will even continue longer than that. I think what we really need is some molecular profile to tell us the biology of the cancer and indicate what the risk of having a recurrence beyond 5 years or beyond 10 years is, so that we can pick or select patients, in a more definitive way, who are really going to benefit from this treatment. So, I think we do it on an individual patient basis. I think it depends on what you think their risk of recurrence is beyond 5 years, but also how they’re tolerating the drug is very important.

Hope S. Rugo, MD: We’re waiting with bated breath for the results of the NSABP B-42 trial. It’s a cleaner study than MA.17R and likely will, in general, have probably randomized more women at higher risk. I don’t know the demographics of that trial yet, and I’m really waiting with a lot of interest in those results. I think that they’re going to help us a lot in understanding the benefit of extending AI therapy after 5 years in a more homogenous population and understanding the risks, as well as which patients are more likely to benefit.

Transcript Edited for Clarity
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