Discussing the Latest Results From the MONALEESA-3 Study

Debu Tripathy, MD:The MONALEESA-3 trial was recently published and presented at the ASCO meeting. This trial was a little bit different than the other trials in that it allowed both first- and second-line endocrine therapy. The endocrine therapy was fulvestrant, and patients were randomized to either placebo or ribociclib at 600 mg a day. This design was motivated by recent data showing that first-line fulvestrant may be a little bit superior to a first-line aromatase inhibitor. This trial, the FALCON trial—the most recent of these trials—was done in patients who had not had endocrine therapy in the metastatic setting. What that trial showed was that overall, the progression-free survival was better with fulvestrant, particularly in patients who had nonvisceral disease.

On that basis, there was an interest in exploring combinations with CDK 4/6 inhibition. This trial enrolled about half of the patients in first line and about half in second line and showed very similar results in terms of the hazard ratios with a doubling of progression-free survival. In fact, it was a little bit better than you would have expected, given the fact that half the patients were receiving treatment in the second-line setting. The toxicity profile was very similar to what had been described before: mostly neutropenia, and just 1% febrile neutropenia. There were a few cases of liver functional abnormalities and QT prolongation, but none that resulted in long-term problems. In fact, there were no clinical consequences of the QTc prolongation.

In the opinion of Dr. Sleiman, who presented the data, the benefit that fulvestrant may have as just a single agent may really make this the preferred first-line therapy for patients in partnership with a CDK4/6 inhibitor, or if one is using endocrine monotherapy. One should use other factors in making these decisions. For example, is there a concern that the patient may not be compliant? Might fulvestrant be a better option, or would the patient be averse to receiving monthly injections? These are other factors that should be used in the decision.

When one is considering a hormonal therapy partner, whether it’s with a CDK4/6 inhibitor or with everolimus, or whether one is considering endocrine therapy alone, I think one has to look at the differences between these agents. The data that we have with fulvestrant compared with aromatase inhibitors, granted, are with single-agent therapy. I think that’s where you can most reliably use the data from the FALCON study: for example, maybe in using fulvestrant first, especially in the patient who has not received endocrine therapy in the advanced setting and who has nonvisceral disease. In that setting, I think one can confidently say which is a better partner.

By extension, one might assume that if you’re combining it with a CDK inhibitor, the same will hold, and fulvestrant might be a slightly better partner. The MONALEESA-3 study provides evidence of that, but not the kind of evidence that you would have with a randomized trial dedicated to that. Those trials are under way. But as clinicians, we have to use the available data to make the best decisions. If I find a patient who really has fulvestrant as an equal option in terms of preferability and injections and whatnot, I would favor that, particularly as the endocrine partner in someone with nonvisceral disease.

Transcript edited for clarity.