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MONALEESA-7: Ribociclib in Premenopausal Women With mBC

Insights From: Debu Tripathy, MD, MD Anderson Cancer Center; Sara Hurvitz, MD, UCLA Jonsson Comprehensive Cancer Center; Hatem Soliman, MD, H. Lee Moffitt Cancer Center & Research Institute
Published: Thursday, Aug 02, 2018



Transcript: 

Debu Tripathy, MD: MONALEESA-7 was a trial that was designed specifically for premenopausal patients, and it has been almost 20 years since we’ve had a trial dedicated to premenopausal patients. And this was a series of trials done and reported back in the early 2000s looking at premenopausal patients comparing tamoxifen alone with tamoxifen with ovarian suppression—in this case, with a drug called buserelin.

And what the results from that study showed is that not only the time to progression was longer, but overall survival was longer. And since that time, it has become the standard to generally use ovarian suppression along with either tamoxifen or, more recently, with aromatase inhibitors or fulvestrant because of that survival difference.

So, being that we now established that ovarian suppression is important, yet all the CDK inhibitor trials and mTOR inhibitor trials were specifically in postmenopausal patients, MONALEESA-7 was designed to suppress the ovaries first and then examine first-line treatment with either an aromatase inhibitor or with tamoxifen with ovarian suppression. The 2 arms were the endocrine partner, either tamoxifen or an aromatase inhibitor, with either placebo or with ribociclib. And the results of that study actually showed very similar progression-free survival and benefit from the addition of CDK inhibitors that is roughly a doubling of the progression-free survival as we had seen in the postmenopausal trials.

But it was very important to do a trial dedicated to premenopausal patients because now we have established 2 things. One is that you get equivalent outcomes in this group of patients if you suppress the ovaries, and we had enough statistical power because the entire population was premenopausal, but we also provided some support for the use of tamoxifen instead of an aromatase inhibitor. And while the study was not powered to look at the benefit in each of these subgroups, I think there’s enough support that at least if you see someone who’s having significant side effects from an aromatase inhibitor, one could consider switching the endocrine partner to tamoxifen.

Hatem Soliman, MD: The impact of the MONALEESA-7 data on clinical practice has been that they have provided us with new information that was limited previously, especially for women who are premenopausal or perimenopausal, which was one of the main focuses of the trial. And so, they were able to generate data in this subset of patients to show that the use of an ovarian suppression strategy with either an aromatase inhibitor or tamoxifen in combination with ribociclib was safe and effective across all those different populations. So, I do think that the impact of the trial was to provide additional options that we could use to better tailor our hormonal partners with a CDK4/6 inhibitor for some of these premenopausal or perimenopausal women when we have to take into account other health concerns or considerations around the therapy.

Sara Hurvitz, MD: The fact that this entire study was dedicated to evaluating the benefit of the CDK4/6 inhibitor in these younger women is, I think, very important for our practices.

It is showing us that the use of a CDK4/6 inhibitor has a similar benefit profile for these younger women compared with the older women. And the safety also appears to be consistent with what we already know about these inhibitors. So, I think it lends the use of support for the use of an aromatase inhibitor or tamoxifen in combination with an LH/RH agonist and ribociclib in this setting.

Now, palbociclib and abemaciclib were both also evaluated in younger women, but it was only about 20% of the patient populations in MONARCH-2 or PALOMA-3. So, again, the fact that this study was entirely in young women gives us really good evidence that it is OK for us to use these agents in our young women.

Transcript Edited for Clarity 
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Transcript: 

Debu Tripathy, MD: MONALEESA-7 was a trial that was designed specifically for premenopausal patients, and it has been almost 20 years since we’ve had a trial dedicated to premenopausal patients. And this was a series of trials done and reported back in the early 2000s looking at premenopausal patients comparing tamoxifen alone with tamoxifen with ovarian suppression—in this case, with a drug called buserelin.

And what the results from that study showed is that not only the time to progression was longer, but overall survival was longer. And since that time, it has become the standard to generally use ovarian suppression along with either tamoxifen or, more recently, with aromatase inhibitors or fulvestrant because of that survival difference.

So, being that we now established that ovarian suppression is important, yet all the CDK inhibitor trials and mTOR inhibitor trials were specifically in postmenopausal patients, MONALEESA-7 was designed to suppress the ovaries first and then examine first-line treatment with either an aromatase inhibitor or with tamoxifen with ovarian suppression. The 2 arms were the endocrine partner, either tamoxifen or an aromatase inhibitor, with either placebo or with ribociclib. And the results of that study actually showed very similar progression-free survival and benefit from the addition of CDK inhibitors that is roughly a doubling of the progression-free survival as we had seen in the postmenopausal trials.

But it was very important to do a trial dedicated to premenopausal patients because now we have established 2 things. One is that you get equivalent outcomes in this group of patients if you suppress the ovaries, and we had enough statistical power because the entire population was premenopausal, but we also provided some support for the use of tamoxifen instead of an aromatase inhibitor. And while the study was not powered to look at the benefit in each of these subgroups, I think there’s enough support that at least if you see someone who’s having significant side effects from an aromatase inhibitor, one could consider switching the endocrine partner to tamoxifen.

Hatem Soliman, MD: The impact of the MONALEESA-7 data on clinical practice has been that they have provided us with new information that was limited previously, especially for women who are premenopausal or perimenopausal, which was one of the main focuses of the trial. And so, they were able to generate data in this subset of patients to show that the use of an ovarian suppression strategy with either an aromatase inhibitor or tamoxifen in combination with ribociclib was safe and effective across all those different populations. So, I do think that the impact of the trial was to provide additional options that we could use to better tailor our hormonal partners with a CDK4/6 inhibitor for some of these premenopausal or perimenopausal women when we have to take into account other health concerns or considerations around the therapy.

Sara Hurvitz, MD: The fact that this entire study was dedicated to evaluating the benefit of the CDK4/6 inhibitor in these younger women is, I think, very important for our practices.

It is showing us that the use of a CDK4/6 inhibitor has a similar benefit profile for these younger women compared with the older women. And the safety also appears to be consistent with what we already know about these inhibitors. So, I think it lends the use of support for the use of an aromatase inhibitor or tamoxifen in combination with an LH/RH agonist and ribociclib in this setting.

Now, palbociclib and abemaciclib were both also evaluated in younger women, but it was only about 20% of the patient populations in MONARCH-2 or PALOMA-3. So, again, the fact that this study was entirely in young women gives us really good evidence that it is OK for us to use these agents in our young women.

Transcript Edited for Clarity 
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