Discussing the Latest Data From the MONALEESA-7 Study

Debu Tripathy, MD:The MONALESSA-7 trial was one that was dedicated to pre- and perimenopausal patients. It has been a long-standing tradition to use ovarian blockade as your optimum therapy when you combine it with an aromatase inhibitor. And so, when the data on CDK4/6 inhibitors and everolimus came out, many physicians would use this approach in their premenopausal patients. They’d use the approved regimen, but they’d use ovarian blockade: either surgical oophorectomy or medical oophorectomy.

However, that still left some room for doubt. Is the biology different in premenopausal patients, even with ovarian blockade? Or if ovarian blockade is started around the time of the initial therapy, would you get the same results? Might you be able to use tamoxifen? These are all questions that were addressed specifically by the MONALESSA-7 study. By enrolling exclusively patients who were pre- or perimenopausal, one had greater statistical power to look at the different subsets, particularly tamoxifen versus nonsteroidal aromatase inhibitors. This trial enrolled the same number of patients, in the mid-600s, randomizing everybody receiving goserelin as ovarian blockade with either a nonsteroidal aromatase inhibitor or tamoxifen to either placebo or ribociclib.

The trial did show similar benefits to what has been seen in the postmenopausal population at roughly a doubling of the progression-free survival with a very similar toxicity profile, as well. It did validate that yes, one gets equivalent results with ovarian blockade. In fact, at the first tumor assessment at 8 months, there was a clear separation of the curves in the ribociclib and placebo groups. About a quarter of patients ended up being on tamoxifen, and when one looks at the progression-free survival differences between the tamoxifen and the aromatase inhibitor group, they were very comparable. While we may not have enough data to just offer tamoxifen, many times in clinical practice, patients have intolerance to the aromatase inhibitor. Now one might find some support to be able to change those patients over to tamoxifen as the endocrine partner.

If one is treating a premenopausal patient, it is important to use ovarian blockade and render them postmenopausal. All of the data we have is in that setting—and certainly if one is using an aromatase inhibitor, that’s mandatory. The short answer is: either an LHRH agonist or surgical oophorectomy.

The data that we have in terms of safety from the CDK and hormonal therapy studies tell us that the safety signals we get are similar regardless of the endocrine partner or the CDK4/6 inhibitor used, with some exceptions. We know that with palbociclib and ribociclib, it’s primarily neutropenia that’s usually subclinical. There’s some degree of fatigue. A few patients do experience hair loss. And then there are rare side effects of liver dysfunction. In the case of ribociclib, the QTc interval has been found to be prolonged. But really, it’s a class effect. You see these in many of the drugs we use in oncology. So far, they haven’t led to clinical adverse effects.

One thing that came up recently in the MONALESSA-7 trial that we really weren’t aware of, as a medical community, is that with tamoxifen alone, there was some prolongation of the QTc time, and this was accentuated with the use of ribociclib. It didn’t lead to any clinical adverse effects, but it is something to be aware of, just like with many of the other drugs we use in oncology, like eribulin and ondansetron. They do prolong the QT interval. Particularly when we’re combining these drugs, we do have to pay attention to that.

Transcript edited for clarity.