Data From the SOFT and TEXT Trials: Combination Therapy With OFS in Breast Cancer

Transcript:
Virginia G. Kaklamani, MD, DSc: That leads me to the question of [the] SOFT [NCT00066690] and TEXT [NCT00963417] [trials]. Moving on from oncofertility and fertility preservation to treatment of breast cancer in these young women and using ovarian suppression as fertility. Walk us through, Matteo, the TEXT and the SOFT trials and how you interpret those results and how you use them for your patients.

Matteo Lambertini, MD, PhD: I think that these have been the 2 key trials to really improve the way we treat in the adjuvant setting our premenopausal women with breast cancer. Just a brief overview on these 2 studies, [which are of] similar design but with some slight difference between [them]. In the SOFT trial, there were 3 treatment arms: tamoxifen alone for 5 years, tamoxifen plus OFS [ovarian function suppression] for 5 years, or OFS plus an aromatase inhibitor for 5 years. The primary objective was to investigate the benefit of adding OFS…to tamoxifen; the comparison between the tamoxifen and tamoxifen plus OFS. Half of the patients received prior chemotherapy, half did not. For those women who received prior chemotherapy, they had to be eligible to be [randomly assigned] in the trial, they had to resume ovarian function within 8 months following chemotherapy, and they had to resume ovarian function—menses coming back or premenopausal hormonal levels [of] FSH [follicle stimulating hormone], estradiol level. And then randomization of tamoxifen, tamoxifen OFS-AI [aromatase inhibitor]. In the TEXT trial, there were only 2 treatment arms, OFS plus tamoxifen [or] OFS plus an AI for 5 years. Again, half of the patients received prior chemotherapy [and] half did not, but those patients who received prior chemotherapy had to start ovarian function suppression before initiating chemotherapy, …as we do for those women who are young and want to preserve fertility and ovarian function during chemotherapy. The overall message that I have from this study is that I have 3 groups, or 3 and a half groups, of patients in this study. One group [of] very clear, low-risk patients; patients with very low risk of disease recurrence. In this case, tamoxifen alone is still standard of care. There is apparently no benefit of adding OFS to tamoxifen or combining OFS [with] an AI. We increase the [adverse] effects without any additional value in terms of efficacy. At the end, for this group, I mostly refer to women who are maybe a bit older, so closer to the natural age of menopause, grade 1, no negative, high hormone central expression. On the other side, I have patients who have a very high risk of these recurrences, much younger, a large tumor, many positive nodes, high proliferative disease, maybe lower expression of hormone receptor. In these cases, I definitely go for the most effective endocrine treatment option I have, which is the combination of ovarian function suppression plus an aromatase inhibitor. Then I have a 1 and a half group, the intermediate risk group, which is the one that is more complicated in terms of clinical practice. In this group, my approach is that, usually, I include ovarian function suppression because we have data that also in this intermediate group [that] there is a benefit in terms of disease survival and also signaling overall survival for the addition of ovarian function suppression. However, I’m not very comfortable discussing tamoxifen vs AI in this intermediate risk group. So what I do in those women who receive chemotherapy, but who I feel have an intermediate risk of this recurrence…I have no preference between tamoxifen or an AI, [but I’m] probably more for [in favor of] tamoxifen because it’s better tolerated than an AI. For the women with intermediate risk but who do not receive chemotherapy for any reason, [there are] genomic testing and other considerations. In these cases, I combine an aromatase inhibitor with ovarian function suppression, because we have some data from the SOFT and TEXT studies, and particularly looking at the score, that this intermediateriskgroup, not receiving chemotherapy, OFS plus AI, appears to perform better. However, this can be discussed. I think that what is very clear is the low-risk patient population and the high-risk patient population, where these treatment options are more clear. But I would love to hear what you do in this setting.

Virginia G. Kaklamani, MD, DSc: That’s similar to our guidelines that are looking at chemotherapy as a marker of risk and saying, “Well, if the patient is at high-enough risk that you’re recommending chemotherapy, then they’re at a high-enough risk that OFS is going to benefit them.” That’s what I typically do. I also use the step analysis to guide me; I don’t know if you do that too. Now at least there’s a nice website that people can go on and they can look at the step analysis and plug in all of the information for their patients. I think this helps me with this risk stratification and gives me an idea of, with the TEXT trial, what is going to be the difference between giving an AI and giving tamoxifen if you’re going to give ovarian function suppression? Are you usually doing the step analysis for your patients?

Matteo Lambertini, MD, PhD: Yes, indeed, I was referring to the score. With this step analysis, it can be freely accessible online. I think it’s very helpful to stratify the risk of recurrence in our patients based on all the factors that we normally use in our clinical practice. So I do use it.

Transcript edited for clarity.