Cases from the Community: Investigators Provide Their Perspectives on the Practice Implications of Emerging Clinical Research — A Special Video SupplementEssential factors to consider when contemplating the use of neoadjuvant therapy
8:35 minutes.
TRANSCRIPTION:
DR LOVE: So the first case, was a young woman, 35 years old, who had a palpable lesion, but it was very small, because it was superficial. The lesion was ER-positive and HER2-positive. It was 1.1 cm. And then there was an adjacent 0.4-cm lesion, both HER2-positive. And the question was in this unusual situation where you had the option to use neoadjuvant therapy but yet it was below the 2-cm cutoff point that at least the FDA defined, the question is, would you use neoadjuvant therapy and, if so, would you include pertuzumab? And we actually found that most of the audience would not use neoadjuvant therapy — would send the patient to surgery and then treat postop. But about half of them would do that. The other half wouldn’t use neoadjuvant therapy, mostly with pertuzumab, including quite a few people on the faculty. How do you think through this situation? DR SMITH: I think both approaches are very reasonable. I am increasingly in favor of the neoadjuvant approach even with the small cancers. And the real issue is not so much the lesion in the breast but it’s the potential for disease in the axillary nodes. And if you can get a pathologic complete remission in the nodes — assume — the problem is, you don’t know whether the nodes are involved or not at this point. But if you treat with the neoadjuvant approach and then the nodes are clear, the sentinel nodes, even if there is scarring to suggest that perhaps there had been disease then, then in my book, that allows the patient to avoid axillary nodal resection and avoid the risks of lymphedema. So to me, that’s a big advantage. And it’s almost more of an issue these days than avoiding mastectomy, which was, of course, the original rationale for a neoadjuvant approach. DR LOVE: I think that’s a really good point. And we did a poster at San Antonio in 2015 about neoadjuvant therapy where we saw this dynamic played out. But one of the things that we saw was that even people who had palpable nodes before neoadjuvant therapy, palpable node-positive disease, what we saw was, in investigators, if the patient had a clinical complete response to neoadjuvant therapy in the axilla, would do a sentinel node. And then if it were negative, no, even with palpable disease. What do you think about that? DR SMITH: Yes. This is what we do. Even if the nodes are clearly involved, even if they’re biopsy proven before we start treatment, we do our best to clip the node from which the biopsy came to make sure we can actually remove that specific node during the sentinel node procedure. And providing there is pathological remission there, even if there’s a lot of scarring, even if you know the node was involved initially, we would not do axillary node resection. But I’ve got to say it’s a controversial area. And I know surgeons who work in other cancer centers around the UK who would feel uncomfortable with that approach. But that’s the way we do it. DR LOVE: And actually we had 30 surgeons that we surveyed for this poster. And in general, that was their algorithm as well. The other thing about this case is the question, okay — if you’re going to use neoadjuvant therapy, are you going to use pertuzumab? DR SMITH: Yes. DR LOVE: The question, I mean, whether you can access it, theoretically, maybe it would be a problem. But would you use pertuzumab? DR SMITH: I think the answer is that if it’s available, we would use it, because why would you not? We know that it increases the potential for pathological complete remission. If you knew for certain that the nodes were negative at the start, then the trial that was run in Boston and in New York and other centers in the Northeast with weekly paclitaxel and trastuzumab as adjuvant therapy in small cancers, that showed extremely good results with only about 2 patients out of 450 relapsing after 5 years. And Eric Winer gave a little mini update when he was talking at San Antonio. And now it’s 8 years, I think, there have been practically no further relapses. And that, of course, is much less expensive. But the problem is in the neoadjuvant approach, you don’t know if the nodes are clear until you sample them. So on the basis of uncertainty, why would you not add in pertuzumab? And that’s what we would do. DR LOVE: Although actually I didn’t think about it. It wasn’t brought up at the meeting. But theoretically, even though generally people do sentinel nodes after neoadjuvant therapy, you could do a sentinel node before neoadjuvant therapy. DR SMITH: Yes. DR LOVE: If it’s negative, I don't know, send them to surgery? I don't know. DR SMITH: The advantage of that is, you save money. But that’s the only advantage, because is the patient happy to have a surgical procedure that probably required anesthetic to save somebody a little bit of money? If I were the patient, I’d probably just want the additional drug. We’re dealing with drugs with very, very minor toxicities. DR LOVE: So another issue about this case is the fact that she was not only HER2-positive but also ER- and PR-positive. And it sort of brings up the issue of the NSABP study that was actually presented at San Antonio — actually it was after the satellite, so we didn’t know the results at that time — where they looked at the idea of using neoadjuvant endocrine therapy in these patients. Can you talk about what was looked at there, what they found and what you think it means? DR SMITH: They, as I recollect — and I don’t have the notes in front of me — what was found there was that the path CR rate with the addition of endocrine therapy to chemotherapy and trastuzumab gave very similar path CR rates. And that is an important observation, because there’s been this concern about using combined endocrine therapy with chemotherapy. And of course standard teaching is that you should not use tamoxifen or letrozole with adjuvant chemotherapy. But that’s based on 1 trial. And there’s another smaller trial that suggests that perhaps that doesn’t happen. That’s always worried me, because there’s a group of patients with ER-positive breast cancer who probably don’t benefit much from chemotherapy, although we give it. That’s changing now that we’ve got gene expression profiling. But nevertheless, there are patients who may get chemotherapy who don’t really benefit from it but who have to wait 6 months to start their endocrine therapy, which could be deleterious. So these trial results, although it’s not what the end of the trial was, as far as I’m concerned, points to the fact that we have to really look at this issue of whether we really have to withhold endocrine therapy until we’ve completed chemotherapy. As far as the trial itself is concerned, it doesn’t improve the pathological complete remission rate, which, of course, was one of the questions in the trial, would it, because pathological complete remission rates for ER-positive cancer, however, are always lower than for ER-negative. And the addition of that doesn’t overcome that issue. DR LOVE: Yes. That was kind of disappointing. I guess I had my hopes up that it was going to show a benefit. DR SMITH: Yes, but it could have been the opposite. It could have shown a lower path CR rate, which would have, of course, vindicated our current approach, but it didn’t. |