Cases from the Community: Investigators Provide Their Perspectives on the Practice Implications of Emerging Clinical Research — A Special Video SupplementDosing and tolerability of pertuzumab
6:33 minutes.
TRANSCRIPTION:
DR LOVE: So another case we discussed at the meeting, presented by Dr Pat DeFusco, was an older patient, 76 years old with a big tumor, 6 centimeters, ER/PR-negative, HER2-positive, nipple retraction, axillary node that was palpable, although the biopsy was negative. This patient was an obvious candidate for neoadjuvant therapy. And the questions that Dr DeFusco had were a couple. First of all, this lady was kind of 76, sort of frail looking, and the question is, is anthracycline necessary? And the other question that she had that I thought was really interesting was that the patient was only 99 pounds. And she brought up the issue of pertuzumab dosing. Obviously you’d want to use pertuzumab in this situation. But she wondered whether or not — the package insert stipulates a flat dose — whether or not there might be any rationale to decrease the dose. Any thoughts about this case and how you manage the frail elderly with locally advanced HER2-positive disease? DR SMITH: The first thing is, I would be very reluctant to use an anthracycline here. This woman already has got important risk factors, not the least age itself, for anthracycline-induced cardiotoxicity. And the very reasonable alternative based on the BCIRG-006 trial would be docetaxel/carboplatin. But even that is quite heavy going for an elderly lady. I might be tempted here — in fact, I would be tempted to use weekly paclitaxel along the lines we were talking about earlier, weekly paclitaxel alone with trastuzumab and pertuzumab and see where we got. And, given the excellent results from adjuvant trials and also given the fact that in the NeoSphere trial 1 arm was trastuzumab and pertuzumab alone — and that achieved a 30% response rate — that’s without any chemotherapy — there would be a reasonable chance that this lady might get a path CR with that very simple treatment, that even someone who’s elderly and frail would tolerate. And then if you didn’t, you have to make a decision after surgery as to whether you were going to give slightly more intensive chemotherapy, introducing, for example, carboplatin after it. So that’s the way I would approach that problem. In terms of whether you reduce the dose of pertuzumab or not, I just don’t know. I guess I’d discuss it with our pharmacy. I’m trying to remember what the general view of the group was. DR LOVE: Actually, the faculty at the meeting was very clear cut that they would not reduce the dose. DR SMITH: Yes. DR LOVE: But no one seemed to know whether there was any documentation or data correlating dose with tolerability issues. It was interesting for me, talking with all these oncologists — we had 12 oncologists submitting cases — over the course of hearing about dozens and dozens of cases. I heard of a number of instances of problems that were thought to be related to — with pertuzumab, particularly diarrhea. DR SMITH: Yes. DR LOVE: Is that your experience? DR SMITH: Yes. For me, when I said earlier that pertuzumab is a very low-toxicity drug, it’s not always. And diarrhea is the main problem. Usually it’s just for a few days and it’s tolerable or you can cope with it with antidiarrheals. But I’ve had 1 or 2 patients who, after 3 or 4 months of treatment, we’ve just had to stop the pertuzumab because of that. Now, what I’m not aware of is whether that is dose related. But you might be just a little anxious. And certainly if I were going to treat this elderly patient, this very small patient, with a standard dose, I would be very cautious and supervise her very carefully and keep in close touch with her about the possibility of diarrhea, because that would not be much fun in a fairly poor 76-year-old. DR LOVE: So another case that was presented — this was from Dr Rich Zelkowitz — I thought this was such a great case. It was a 53-year-old lady, again ER/PR-negative, HER2-positive tumor, who actually refused neoadjuvant therapy. And I don't know how often this happens, but he was just saying she just wanted to go right to surgery regardless of what he said to her. So she did go to surgery and, in fact, was found to have a two and a half-cm node-negative tumor, again, ER-negative, HER2-positive. And his question was about the use of adjuvant pertuzumab. Now, this patient fits into the category that the NCCN discussed of the patient could have been eligible for neoadjuvant therapy, because the tumor was greater than 2 centimeters but now is presenting postop. So the question was, would you use pertuzumab, and if you would use it, would you use it only during chemotherapy/trastuzumab or out for a year? And we actually saw a spectrum of answers. We saw a couple of faculty people said they would not use pertuzumab. Several would, mostly during chemotherapy. How do you, and of course there’s payment issues, reimbursement questions that come up. But what makes the most sense to you clinically in terms of what to do in this situation? DR SMITH: No. I think if pertuzumab were available, then I would use it — just out of interest for you and your colleagues in the States, the current funding for pertuzumab in the UK is only for neoadjuvant treatment. And that’s based on the NeoSphere data and the follow-up, which shows that there is an improved outcome. But we don’t yet have the results of the APHINITY trial, which is the definitive trial to tell us about the role of — so that’s where the UK legislators come in. And, in fact, it’s fairly logical on the basis of evidence. But if it were available, why would I — yes, I would use it. Why not? |