HR+ Breast Cancer: FALCON

Transcript:Adam M. Brufsky, MD, PhD: So, we’re going to turn now to hormone receptor-positive metastatic breast cancer, and start with data that are being presented at ESMO 2016, and go from there. Michael, the FALCON trial is being presented actually today at ESMO. Can you start with that and explain that to us?

Michael Untch, MD: Yes, thank you, Adam. The world is moving really quickly. Actually, I’m part of the National Guideline Commission in Germany. We just finished, 6 months ago, the update in which still, for the moment, first-line treatment in patients with metastatic hormone receptor-positive disease is an aromatase inhibitor. The FALCON trial is going to give us a new answer on how to treat these patients because the comparison was, in this prospectively randomized trial, fulvestrant with an aromatase inhibitor. And, to make a long story short, fulvestrant is superior in terms of time to progression compared to the standard of therapy at the moment, an aromatase inhibitor. So, I think in this round here, we have to answer some questions because probably that will be the new standard of care for first-line metastatic hormone receptor-positive patients. And I was talking to Ahmad before. Because the trial is so new, I think there were 114 patients on the trial who had already had a previous endocrine treatment. Okay, you are shaking your head.

Hope S. Rugo, MD: FALCON allowed no prior endocrine therapy in any setting.

Ahmad Awada, MD, PhD: For metastatic setting?

Hope S. Rugo, MD: No, in any setting. They couldn’t have endocrine therapy in adjuvant or metastatic setting.

Michael Untch, MD: Excuse me, for adjuvant, correct?

Hope S. Rugo, MD: There were some patients who had previous chemotherapy in the adjuvant setting, but no endocrine therapy.

Adam M. Brufsky, MD, PhD: Now, how does that compare to the FIRST trial where there was a survival benefit?

Hope S. Rugo, MD: Remember, FIRST only had a primary endpoint of the clinical benefit, right?

Adam M. Brufsky, MD, PhD: Right.

Hope S. Rugo, MD: And so, the endpoints of survival were something that were added on later. Those patients also were not supposed to have any endocrine therapy in the metastatic setting. FALCON is a more controlled group with the prospectively defined primary endpoint. So, it takes over.

Adam M. Brufsky, MD, PhD: But, how many people really fit FALCON? How many patients fit FALCON? No endocrine therapy ever? That’s de novo disease.

Hope S. Rugo, MD: If you look at the fulvestrant/anastrozole study, in the US SWOG trial of fulvestrant/anastrozole versus anastrozole, 40 some percent of patients had de novo metastatic disease. In PALOMA-1, it was a little more than 40%. In PALOMA-2, it’s about 40%. In the MONALEESA trial, it’s 30 some odd percent. So, we definitely are seeing these patients.

Adam M. Brufsky, MD, PhD: Really? It just doesn’t seem to be my clinical experience.

Hope S. Rugo, MD: No, me neither, but the trials are.

Michael Untch, MD: Okay, Adam, that was the reason right before I asked Ahmad, where are these patients? How often are we seeing them? Because, I face the other problem. I see patients on the current endocrine therapy like ER4 breast cancer on aromatase inhibitor and they develop coughing, pleural effusion, metastatic breast cancer. Now, those patients would not fit into this trial here because they are, per definition, endocrine resistant.

Adam M. Brufsky, MD, PhD: So, how do we treat those patients?

Hope S. Rugo, MD: Let me just ask you about FALCON again, though.

Michael Untch, MD: I know that this is very contradictory now.

Hope S. Rugo, MD: Well, you said that FALCON would then result in a change of the standard of care, which is interesting to me because the FALCON data showed an improvement in PFS in the population as a whole that was modest. The big improvement was in patients who had bone and soft-tissue disease, so node and bone are where the improvement was quite significant. But, if you compare that data to what’s seen in the PALOMA-2 and MONALEESA trials, that was all-comers. In both trials, almost half of the patients or more, more than 50% I think in both trials, had visceral disease. So, you’re looking at adding on a CDK4/6 inhibitor to an AI that really increases the PFS in patients who have the worst disease prognostically, and then you’re comparing that to a subgroup of patients who have bone and soft tissue disease where we know they do well. Maybe what we’re really understanding is that in those patients who have very endocrine-sensitive disease, fulvestrant may be superior to an AI and that’s what it appears to be from FALCON.

But, in the population of patients who were relapsing or patients who have visceral dominant or just visceral disease, those patients probably don’t have that difference.

Michael Untch, MD: We have to repeat this because that was kind of a provoking statement from me.

Adam M. Brufsky, MD, PhD: It is a provoking statement, which is good. Very provocative, that’s the way it should be.

Michael Untch, MD: Yes. I try to make a consensus here, the “Copenhagen consensus”. So, in endocrine-sensitive metastatic disease, Hope, these data are convincing enough to replace the aromatase inhibitor by fulvestrant, yes or no?

Hope S. Rugo, MD: So, for me, I think yes, fulvestrant is a good option. Do we know what the sequencing has? We don’t know. We need a little bit longer term data from this trial. If they showed a survival benefit, it would be huge. I think that it’s a good option, and, in a certain segment of patients who never had any prior endocrine therapy and have bone and soft tissue disease, it appears to improve progression-free survival. But, it does involve coming in every month for an injection. A pill, you can take anywhere. But, an injection, you’ve got to come in to the clinic for. You have to balance every decision against that benefit. I have to say, fulvestrant is not going to cause the joint pains and some of the other sexual side effects seen with AIs, so those may be some additional benefits that make it even more appealing for patients who have this subset of bone-only or bone and soft tissue-dominant disease. I think saying it is standard of care is a little bit too much at this point.

Transcript Edited for Clarity