Cases from the Community: Investigators Provide Their Perspectives on the Practice Implications of Emerging Clinical Research — A Special Video SupplementMINDACT trial: Utility of the 70-gene signature in selecting patients with BC for adjuvant chemotherapy
8:24 minutes.
TRANSCRIPTION:
DR LOVE: So I want to go on and ask you about another case that was presented at the meeting, a 71-year-old lady who actually had ER-positive, HER2-negative disease but 3 positive sentinel nodes. And this patient actually had had a 70-gene signature assay done that was read out as high. But the doc, if you remember, was confused about how to even look at a 70-gene signature. She mentioned the fact that the MINDACT trial integrated Adjuvant! Online. Adjuvant! Online is not available anymore. So there was that question. When we actually asked the audience in general about this issue of using genomic assays in patients with node-positive disease, what we found actually is that a lot of people are using genomic — we actually said 1 positive node specifically. And we found that a lot of people and investigators are using it, more the 21-gene Recurrence Score, but some either 70-gene or 21-gene and a few preferring a 70-gene. So maybe you can just kind of comment a little bit about the issue of the 70-gene, the 21-gene, node-positive and this doc’s question of, like, how do you look at the 70-gene without Adjuvant! Online around? DR O’SHAUGHNESSY: Mm-hmm. The Adjuvant! Online is actually relatively easily translatable to the anatomic staging that would tell us what a clinical high is. And in the paper that was published, the MINDACT paper, there’s a really nice table that kind of spells out what really are the clinical characteristics that will get you to a high Adjuvant! Online. It’s basically tumor size, grade and nodal status, et cetera. So it’s not difficult to figure out what is clinical high risk. But then, of course, we have the discrepancy, because they may have 3 positive nodes, but the grade may be Grade 2. And if there is a Ki-67 obtained, it may be low. It may be a 10%. And you’re looking at the 71-year-old going, “Gee. Really, what is the absolute benefit that this woman might get from chemo?” And patients ask that. Patients really do want to know what we would estimate their absolute benefit might be so that they can factor that in. So in the 1 to 3 node-positive group — that was the group that was studied in the MINDACT along with the node-negative, higher-risk node-negative patients — it’s not unreasonable, in my mind, to order a genomic assay if you’re in doubt about the benefits from chemotherapy, like the situation where the Ki-67 is very high, it’s high grade, there’s lymphovascular invasion. If you’re not in doubt about the need for chemotherapy, I don’t think there’s a reason to order a genomic assay. But I do order them in the 1 to 3 positive nodes when I’m in doubt. And so I think the MINDACT data are quite reasonable. It’s prospective data, randomized data, randomized clinical trial data. And my takeaway from it is that if a woman is anatomically a bit higher risk, nodes positive, larger tumor size and historically we would have considered chemotherapy for her just based on her nodal status, 3 positive nodes, that if her 70-gene score comes back low and that result is consonant with what I also know biologically about her cancer — it’s Grade 2. It’s strongly estrogen/progesterone receptor-positive. The Ki-67 is not 50%. It’s 20% or less, or something. If it’s consonant, I will say to her that the data from the MINDACT basically in my mind pretty much rule out that she would get more than a few percentage points’ absolute improvement in her disease-free survival. The MINDACT did not say there would be zero benefit from chemotherapy, because there’s always some confidence intervals around point estimates. There’s always a little bit of variability in these estimates. But it rules out an absolute benefit, in my mind, of a 10%. You couldn’t rule out that there might be 2%, 3%, 4% improvement in disease-free survival with the numbers in the MINDACT, but I think it is saying that if a woman decided that she did not want to incur the toxicities of chemotherapy that she’s very likely not disadvantaging herself in terms of her overall outcome. So that’s my interpretation. I actually think the same thing with the 21-gene Recurrence Score as well. The Plan B, very nice publication in the JCO, really is quite reassuring that if you have a low Recurrence Score and 1 to 3 positive lymph nodes, that patients’ outcomes do very well over the first 5 years. And we know that most of the chemotherapy benefit occurs in the first 5 years, although in Kathy Albain’s trial in 1 to 3 — when she looked at the 1 to 3 node-positive subset, there was a chemotherapy benefit that did emerge between year 6 and 10. So I think, though we don’t have randomized, prospective data yet with the 21-gene Recurrence Score, I think that the registry, the large prospective registry-type data are also looking quite reassuring. And I do order the tests, Neil. And if the woman comes to me as a second opinion consult, having had these tests ordered, I do factor them into the discussion. DR LOVE: So just to clarify, though, in terms of the data that we’re drawing from here, with the 70-gene, my understanding is that the hope is that you’ve identified a group with a very low risk of distant recurrence but it’s not that clear whether or not they’d benefit from chemo, but it’s a prognostic thing. Whereas with the 21-gene, it’s both prognostic but also, to some extent, given the caveats of the way the data is analyzing, predictive of benefit. I mean, you can choose which one you kind of like better. But is that an accurate reflection of the data? DR O’SHAUGHNESSY: Yes. I think that is a fair way of saying it, because you’re — and it’s true, though, even with the 21-gene and the 1 to 3 node-positive group — because again, the Plan B the 1 to 3 node-positive group that had a low Recurrence Score and just took endocrine therapy, they did so incredibly well that their prognosis was so good it was — you couldn’t see whether they would get very much, if any, benefit from chemotherapy. Kathy Albain’s trial — again, small numbers, if you get into the intermediate and high Recurrence Score patients in the 1 to 3 node-positive group — in the high Recurrence Score, there was a very definite predictive benefit from chemotherapy there. But the intermediate, the numbers are small and there really wasn’t an obvious benefit from chemotherapy there. But on the other hand, probably at the end of the day there probably will be some benefit in that group, Neil, once we have enough numbers. So we’re still limited in terms of the predictive power of the Recurrence Score in the 1 to 3 nodes. I mean, I think the data are much more in the node-negative. But in the MINDACT trial, we didn’t see predictive power coming out for chemotherapy in the MINDACT. But you’re right. I would say the data were more reassuring from a prognostic standpoint. |