The landmark TAILORx trial has dramatically changed the way patients with estrogen receptor–positive cancer are treated. Continued analyses from the trial have further stratified clinical risk for a subset of women who are 50 years or younger, based on their OncotypeDX Breast Recurrence Score.
ONCOLOGY® recently sat down with Jane L. Meisel, MD, of Emory University School of Medicine in Atlanta, Georgia, to discuss how these data from the TAILORx trial validate and inform the current and future care of patients with breast cancer.
Q: Can you give us some background on the TAILORx trial?
Meisel: It helps to talk first about what oncotype is. Essentially, it’s a genomic test that takes a woman’s tumor after it’s been removed from her body and analyzes it to look at the levels of expression of different genes. If you have high levels of expression of high-risk genes, genes that portend a poor prognosis or a high risk of recurrence, then your oncotype score is higher. And if you have higher levels of expression of low-risk genes, your score will typically come back lower. The score is on a continuum.
The test has been validated for a long time, and we’ve known for a long time, as a clinical community, based on large studies, that if you have a very low oncotype score—like 10 or below, then you really don’t benefit from chemotherapy. If you’ve got an early-stage, lymph node– negative breast cancer, you can get away with antiestrogen therapy alone and not get chemotherapy and still have a great outcome. Conversely, if you have a high-risk score, typically defined as 26 or higher, then you do benefit from chemotherapy in addition to endocrine therapy.
This has been really helpful. You know that if you have a high-risk score, you need chemo, and if you have a low-risk score, you don’t need chemo. However, the vast majority of scores fall in the intermediate-risk category, between 11 and 25. [In these cases,] you have to take into account the patient’s preferences, the doctor’s estimation of risk, and [many other factors] to make a decision about chemo or no chemo. The TAILORx trial was designed to take a closer look at that intermediate-risk group. It randomized those women to receiving chemo in addition to endocrine therapy, or to receiving just endocrine therapy, and looked at outcomes to try to answer, essentially: Can those women get away without having chemotherapy? Do they all need chemotherapy? Or can many of them get away without it? Is there perhaps a subset of women who might benefit from more aggressive treatment?
Q: What were the main findings?
Meisel: This was a landmark trial that has changed our practice [to a substantial degree. The results showed] that the vast majority of women who have risk scores between 11 and 25 did not benefit from chemotherapy. They did just as well when they received antiestrogen therapy alone.
However, the primary results of the trial, when the initial trial was published, showed that a group of women under 50 years who had scores between 16 and 25 may benefit from chemotherapy in addition to endocrine therapy. So, when these data were first presented, and then subsequently when additional analyses were done, a lot of thought was put into [pinpointing] who [exactly] are these women under 50 who might still benefit from some chemotherapy? How do we determine who they are, as best as possible, so that we give the right treatment to the right woman? You don’t want to withhold chemotherapy for someone who needs it, and for whom it might make the difference between cure and not cure. But you also don’t want to give chemotherapy to a lot of people who don’t need it. I think those challenges, particularly in the current coronavirus [disease 2019] era that takes into consideration other risks, really highlight the need to make these decisions.
Q: Can you discuss the trial’s impact some more?
Meisel: The fact that this study looked at thousands of women prospectively, meaning it randomized large numbers of women to one treatment or another, allows you to really have faith in the integrity of the data. This trial was looking at noninferiority: trying to make sure that the regimen of withholding chemo [and giving] endocrine therapy alone was not inferior to a regimen including chemotherapy. The fact that the results were so unequivocal for this large group of women, especially postmenopausal women over 50 years—that they did not need chemotherapy anymore—has really made a huge difference.
Q: Do you have any specific examples of that impact, patients who were directly affected by the results?
Meisel: When this trial was presented at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting, I had a woman in my practice in Atlanta who had an intermediate-risk score—in the low 20s, I think—and she was just over 70 [years] and really did not want to do chemotherapy. Before the TAILORx trial, a score in the low 20s for women, even for a woman of 70 who was in good shape, would be a situation in which we talked about benefits and said, “Well, you could withhold chemo, but we don’t really know yet because we’re waiting for the results of this trial.” So, I said to this patient, because I knew we were going to have these answers in a few weeks, “Why don’t I call you after ASCO and I’ll let you know what these results show?” [She agreed,] and when I called her the day after that presentation and told her, “You don’t need chemotherapy,” it was the happiest day of her life.
She [ended up being] the subject of a layperson’s piece in the Atlanta Journal-Constitution, which my patient loved, but it really was a meaningful moment for her. And there are so many other women like her who [are] now going to make this decision to withhold chemotherapy in very good faith based on data from thousands of patients. And I think we can talk lots and lots about data and hazard ratios and P values, but, you know, for each woman who gets to make a treatment decision, and can do so without having to look back, this can mean the world.
Q: How have the results affected treatment decisions when it comes to the patient-physician conversation?
Meisel: Before TAILORx, we were telling many, many women who had intermediate-risk scores that we were all anxiously awaiting the results of this huge trial, but that until we [had those results], we really had to think about risks and benefits, your preferences, all these things, as we make this decision about whether to give chemo or withhold it. Once we had the study results, though, for many women, particularly those over 50, that decision became a lot more crystal-clear. For women under 50 [with an] oncotype score of 15 or less it also provided a lot of clarity, because those women also do not need chemo. For those women who still remain in a gray zone—women under 50 with scores between 16 and 25—the question wasn’t answered unequivocally, but the results did give us a lot of data with which to enhance our conversation.
Q: For women under 50 years, what was the importance of this kind of exploratory analysis?
Meisel: We know from lots of experiences and lots of studies that, unfortunately, younger women who get breast cancer tend to have more aggressive breast cancers. So this finding in the initial TAILORx trial data that in the overall population [generally, women] with a risk score under 25 don’t need chemotherapy, but that a subset under 50 may benefit, underscores the fact that maybe we do not want to be so quick to withhold chemo from all of these women. A subset of the population may actually get benefit from it. So, we’ve got to be careful. To look more closely at that subset of almost 3000 women under 50, the authors divided those women with recurrence scores between 16 and 25 into 2 groups: clinically high-risk versus clinically low-risk. They then looked at their Oncotype scores along with that and tried to determine whether [that should] impact the decision making at all. That’s something that we were doing in clinic anyway, because as we take into account the recurrence score, we’re also looking at other factors: Was their tumor, for instance, 7 mm or 3 cm? Was it grade 3 or grade 1? But, now [we have some codification] by defining clinically high-risk and clinically low-risk. It was found that women with an Oncotype score between 16 and 20 who were clinically high-risk actually did benefit from the addition of chemotherapy. Those with the same score but who were clinically low-risk didn’t benefit from the chemo. So that further identified a group of women under 50 years, with that high intermediate score, who may not need the chemotherapy.
Q: Can you cite another case where the impact of these findings has emerged in clinical practice?
Meisel: Absolutely. We use these data all the time in practice; they are a wonderful tool to have at our disposal. For example, a patient I had was 45 years old and came to me with a 1.6-cm tumor, grade 2. Her recurrence score was 22, and she really did not want to do chemotherapy—come in for infusions, lose her hair, [none of it]. Her mother had had chemotherapy for a different type of cancer and had had a horrible experience. [On the other hand,] this patient had 2 young children, a job, lots of things she wanted to do in life, and she wanted to reduce the risk of her breast cancer as much as she could.
So, we talked. I presented a few different options for chemotherapy regimens to her because in the TAILORx trial, the women who received chemotherapy got actually a variety of regimens: About a third received anthracycline, and just more than 50% received docetaxel cyclophosphamide, and there was no difference seen [in outcomes] in terms of the chemotherapies provided. She still was not [happy] about it and asked what other options she had beyond tamoxifen. So, I talked to her about the fact that she was still menstruating regularly, and that we thought that some of the benefit of chemotherapy might be in the form of ovarian suppression.
We discussed probably being able to give her some benefit just by ovarian suppression if she wasn’t willing to do the chemotherapy. I felt ovarian suppression made absolute sense for her, if we were going to withhold the chemotherapy and still be as aggressive as possible. So, she started leuprolide acetate (Lupron) and tamoxifen, and then after 3 months she transitioned from the tamoxifen to an aromatase inhibitor. She’s been doing really well with that combination and I think she feels good about the decision she made, being true to herself and her desire to not receive chemotherapy if she did not have to. We were able to do the ovarian suppression and tailor the treatment plan to be as aggressive as she wanted it to be, with data to support it.
Q: From a clinical standpoint, what is one of the most important points physicians can take away from these data?
Meisel: I think the big plus is that these data add a lot of clarity for this population. For women who have an early-stage, node-negative, estrogen-positive breast cancer, the data give us a lot of good information about what should we do for these patients in terms of chemotherapy versus no chemotherapy. And as I mentioned in the previous patient case, if people don’t want to do chemotherapy, we can do more in terms of antiestrogen therapy to help them. Even for the women who are still in that gray zone, a lot of meat has been added to the substance of that treatment conversation.ν
Financial Disclosure: The author has no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.