Adam M. Brufsky, MD, PhD, FACP: I just want to talk a little bit about the SOFT and TEXT trial updates that we have, which are really trying to guide our therapy of these pre- and perimenopausal women who are still menstruating after their therapy. You want to summarize those data, Komal?
Komal Jhaveri, MD, FACP: Well, let’s break it down to SOFT and TEXT separately. The SOFT trial was trying to see if there was a role for adding ovarian suppression to endocrine therapy. So, they randomized patients to 3 arms: to get tamoxifen alone; tamoxifen with ovarian suppression; or an AI [aromatase inhibitor], in this case exemestane, with ovarian suppression.
The TEXT trial looked at, if you are giving ovarian suppression, which ovarian suppression endocrine partner would you choose? Is there superiority in using tamoxifen or an AI? What we saw were the updated results that were presented, and this was a median 8-year follow-up. The primary endpoint in the SOFT trial was to compare ovarian suppression on tamoxifen alone. It did show that when compared with tamoxifen alone, there was a benefit deriving from ovarian function suppression, especially in women who are high-risk and requiring chemotherapy anyway. But in patients who did not require chemotherapy, low-risk patients who were not required to get adjuvant chemotherapy to begin with, tamoxifen alone remained superior in that follow-up study.
When the combined TEXT trials looked at tamoxifen plus ovarian suppression with exemestane, they showed that there was a benefit to utilizing exemestane plus ovarian suppression compared with tamoxifen. The benefit was about 4% overall, and in the high-risk node-positive population, it was even larger than that.
Adam M. Brufsky, MD, PhD, FACP: The bottom line to this is that if you have someone who is at high enough risk, if they got chemotherapy and they’re still menstruating, they still should get LHRH suppression. The bigger question is, what partner do we add? What you’re saying now is an AI.
Hope S. Rugo, MD: The other thing that was really striking to me about the combined data was that women who were under the age of 35 had this enormous benefit.
Adam M. Brufsky, MD, PhD, FACP: That’s a bigger difference.
Hope S. Rugo, MD: There was over a 15% difference in disease-free survival in patients who got an AI plus OS versus tamoxifen, and then an 11.5% benefit in patients who got tamoxifen plus OS. So, what that means is that you can give patients either option. If they can’t tolerate the AI and they’re miserable, or if you want to start with tamoxifen and switch to an AI, that’s OK. You have a huge benefit, and so I really try and get my younger patients on it, obviously those under 35, but it’s probably the same for a 35- or 36-year-old if they have good ovarian reserve. So, that to me is the most impressive part of the data.
Komal Jhaveri, MD, FACP: I agree.
Adam M. Brufsky, MD, PhD, FACP: As we said before for the metastatic setting, is there fear that you’re not suppressing people enough with LHRH plus an AI, that they counteract each other?
Hope S. Rugo, MD: Yes. One of my patients on SOFT who went on OS plus exemestane, and the OS was triptorelin, started up her menses again 6 months into it after finishing the chemotherapy.
Adam M. Brufsky, MD, PhD, FACP: That happens.
Hope S. Rugo, MD: Then she was called a failure on the trial. But I think we do have to monitor these patients very carefully.
Francisco Esteva, MD, PhD: I do monitor them. What Komal said is right. It’s a 4% difference between exemestane ovarian suppression compared with tamoxifen.
Adam M. Brufsky, MD, PhD, FACP: Tamoxifen alone or tamoxifen OS?
Francisco Esteva, MD, PhD: No, tamoxifen without ovarian suppression.
Hope S. Rugo, MD: Alone.
Francisco Esteva, MD, PhD: But that was the update in San Antonio.
Hope S. Rugo, MD: From TEXT.
Francisco Esteva, MD, PhD: But that was for breast cancer disease-free survival in a way, where if you look at the distant disease-free survival, it was only 2%. In my experience, the combination of an AI plus ovarian suppression was a little more toxic than tamoxifen plus ovarian suppression. So, that was 2%: from 90% to 92%, very small.
Hope S. Rugo, MD: So, you really have to balance the quality of life.
Adam M. Brufsky, MD, PhD, FACP: A lot of people come off this. In that trial, how many people came off? Was it around 40% after 2 years?
Hope S. Rugo, MD: It was 30-something percent.
Komal Jhaveri, MD, FACP: It was 20% at 2 years and about 40% at 4 years.
Adam M. Brufsky, MD, PhD, FACP: We’re already making women miserable enough with LHRH suppression. We make them more miserable with an AI on top of it.
Francisco Esteva, MD, PhD: I saw a patient last week who I’m treating with ovarian suppression. She’s 50, and we started with ovarian suppression and tamoxifen. We talked about this, tamoxifen versus an AI. It came down to the quality of life, and we are trying tamoxifen to see how she responds.
Hope S. Rugo, MD: And the thing is, people get used to therapy. Sometimes you can get 2 or 3 years with an AI, and at some point, all of the studies that we’ve done show that getting an AI makes a difference. The Early Breast Cancer Trialists’ Collaborative Group showed that, too. I’m sure it’s going to end up with the compliance that we’ve seen and be the same for premenopausal women. So, you don’t have to actually keep people on this forever, even for 5 years with the AI.
Komal Jhaveri, MD, FACP: I think the long-term data are going to be very, very relevant. I think we have the 15-year follow-up from the time of diagnosis with the ATLAS trial to look at 10 years of tamoxifen versus 5 and the overall survival benefit that we’ve seen balancing out with the risk. We do see a trend in overall survival based on the data that were presented with a median follow-up of 8 years, but we still have to see the overall survival data.
Francisco Esteva, MD, PhD: But the survival was the same though.
Komal Jhaveri, MD, FACP: More important are the safety data for long-term ovarian function suppression, especially in the women with 30s and 40s.
Lee Schwartzberg, MD, FACP: But there was a higher incidence of fractures. The other thing that SOFT and TEXT show is that clinicians are very good at picking who needs chemotherapy versus not because the ones who didn’t get chemotherapy had excellent disease-free survival on tamoxifen alone and there was no benefit.
Adam M. Brufsky, MD, PhD, FACP: Now we have genomic assays to help us even more with that.
Francisco Esteva, MD, PhD: But again, the overall survival was the same.
Adam M. Brufsky, MD, PhD, FACP: Well, that’s the point. The bottom line is if most of what you prevent is local recurrence or new cancer in the other breast, which count as DFS events, the overall survival would probably be the same. If you’re preventing distant recurrence, the overall survival will be changed.
Lee Schwartzberg, MD, FACP: Yes.
Hope S. Rugo, MD: It’s an early time.
Komal Jhaveri, MD, FACP: It’s an early time.
Adam M. Brufsky, MD, PhD, FACP: Right, it’s too early. I agree.
Komal Jhaveri, MD, FACP: I think it needs more follow-up.
Lee Schwartzberg, MD, FACP: Even 8 years, since that was the criticism of SOFT and TEXT. They were presented at a median of 3 years.
Adam M. Brufsky, MD, PhD, FACP: Correct.
Lee Schwartzberg, MD, FACP: Before even half of the events.
Adam M. Brufsky, MD, PhD, FACP: Correct, agreed.
Komal Jhaveri, MD, FACP: I think we need 15 or 20 years.
Transcript Edited for Clarity