Expanding Therapeutic Options for Breast Cancer - Episode 9

Clinical Data on Extended Adjuvant Therapy in HR+ BC


Joyce A. O’Shaughnessy, MD: Let’s get a snapshot of where everybody’s at with regard to extended adjuvant therapy in their practice. We heard some good updates at the ASCO Annual Meeting in the premenopausal population. Where are you with extended endocrine therapy in your practice, Sara?

Sara A. Hurvitz, MD: The big picture is that there have been 5 studies and/or published articles that have looked at longer therapy versus shorter therapy with respect to aromatase inhibitors. When we’re just talking about tamoxifen, 2 studies have now shown significant improvements in overall survival with 10 versus 5 years. But when it comes to the AIs, is 5 years long enough? Four out of 5 of the studies have shown no significant benefit with prolonged therapy.

One study, MA.17R, showed benefit. The majority of the patients had already taken tamoxifen before they went on and got 5 years of AI, and then went on to get either placebo or 5 more years of AI. It really was a 10- versus 15-year study in a very rare group of patients who could take 10 years of therapy and then be randomized to a study for another 5 years.

In my practice, I am not using extended therapy for a majority of my patients. There are some patients in whom we’re just waiting for the other shoe to drop. They have such high-risk disease and they are tolerating it really well and want to continue on. They do so without a lot of data supporting it. So far, none of these studies have shown a subset, or a clinical factor, that would predict who’s going to benefit from the use of extended therapy.

On the other hand, the SOFT/TEXT data were updated this year at the ASCO Annual Meeting. Again, these show that there can be a real substantial benefit with the use of ovarian suppression endocrine therapy in our younger women who are higher-risk. So, it’s supporting the earlier data, but it’s all about selecting the patient. A patient who has lower-risk disease—regardless of the fact that they’re premenopausal, you’re going to give them more side effects with an LHRH and an AI, versus just doing tamoxifen. These are very long discussions that we have with our patients when determining how aggressive we want to be.

Joyce A. O’Shaughnessy, MD: That update was really important. We waited so many years in trying to understand the role of LHRH agonists in the premenopausal group. Looking at the 10% to 15% absolute improvement with the aromatase inhibitor plus the LHRH agonist, compared with either tamoxifen alone or the LHRH agonist plus tamoxifen, and knowing how difficult it is for the women to get the LHRH agonist and the AI, but knowing that when we have that high-risk biology, we should push it. We have to push it. If you’ve got that grade 3 node-positive, PR-negative, high Ki-67 case, they’ve got to have an AI.

Hope S. Rugo, MD: I do still think that the most critical part of this is ovarian suppression. For some patients, giving the AI is really, really tough.

Joyce A. O’Shaughnessy, MD: It’s impossible.

Hope S. Rugo, MD: You could use tamoxifen for the first couple of years in those patients. We’re looking, over time, and they just do better with the tamoxifen upfront. Then, they can switch to the AI. They get more depressed on the AI and have all of the other AI-related symptoms. You have to kind of vary it. For the really high-risk patients, I always try to get them on the AI upfront. But, you have to keep them on endocrine therapy. I think that’s the most important thing.

In terms of duration, it’s interesting because this was 7 years versus 10 years. They said that there was no benefit in 10 versus 7 years, and there were more fractures. But I’ve used that in patients who have higher-risk disease, in order to justify giving 7 years, like a little bit more.

Komal Jhaveri, MD: FACP: Well, I think they should. In that dataset, if you look at it, about 65% to 70% were node-negative. These were relatively smaller tumors. These were node-negative cancers. In that patient population, I agree. I have applied this dataset in a similar way. If this patient has node-positive disease and is tolerating the treatment well, and I know it’s confined and there is adherence, then I would be tempted to continue beyond the 7 years.

Hope S. Rugo, MD: Well, for the high-risk patients, we ought to continue with something.

Sara A. Hurvitz, MD: None of those high-risk patients who are going to recur in the first 5 years are represented in these datasets, right? They’re all randomized after having 5 years of endocrine therapy with no event. So, it’s not helping us decide the approach to take.

Joyce A. O’Shaughnessy, MD: Yes. I call it the B-42 bakeoff. The Breast Cancer Index, EndoPredict, etc, will hopefully help us. We need some way to really identify those patients who are at risk for later recurrence, but who may also benefit from extended adjuvant therapy.

Hope S. Rugo, MD: What you’re talking about is the trial population that has already been presented.

Joyce A. O’Shaughnessy, MD: Yes.

Hope S. Rugo, MD: Where the tissue was collected in NSABP-style. Where there will be analyses done by different genomic tests to see if there’s a subgroup who benefits from therapy. This will be fascinating, but it’s probably at least 2 years away.

Transcript Edited for Clarity