INTERVIEW WITH DR. MICHAEL BAUM

DR. LOVE: Let me come back to ask you one more thing about the ATAC trial. I take it from the fact that you already put one of your patients on anastrozole that you consider that a non-protocol option at this point in some patients.

DR. BAUM: Yes

DR. LOVE: What about the woman who presents for treatment with an ER positive tumor who is premenopausal who gets chemotherapy and at the completion of her chemotherapy is amenorrheic.

DR. BAUM: Well, then that's off protocol, it is purely speculative it should be left at the discretion of the clinician. He or she has to be aware that there are no data to support that choice.

DR. LOVE: Any reason to think one way or the other what the effect would be?

DR. BAUM: I think in theory that chemotherapy or gonadotrophic releasing hormone, making a woman amenorrheic, is like making her like a post menopausal woman, and there may indeed be a place for anastrozole in that setting. But, I would love to see a trial rather than everyone rushing into it.

DR. LOVE: What are some of the trial ideas, or questions that you think are very important to pursue, what are some of the ones that you want to pursue right now?

DR. BAUM: There are a number of trials involving aromatase inhibitors that will be facing the difficulty we're facing in their design about continuing the tamoxifen arm, up to the point of crossover. So, there are problems with those. The one I would particularly favor is preoperative or perioperative endocrine therapy and there is an excellent biological rational for that, which I won't go into for the moment. But a feasibility study of that type is already under way. It is called Impact and it's being conducted at Royal Marsden Hospital. It has the added advantage in that you can take biological samples of the primary tumor in the preoperative phase, in order to study what's happening at the cellular level, in the face of the aromatase inhibitors.

DR. LOVE: But isn't that anastrozole vs. tamoxifen?

DR. BAUM: The IMPACT trial is like the ATAC trial except it is preoperative. That's really as a biological experiment. The ideal design would be anastrozole up front followed by adjuvant anastrozole vs. adjuvant anastrozole. That would be a very nice study. Assuming, presupposing that the early ATAC trends persist.

DR. LOVE: The last time we talked in Miami you talked about doing a trial of best arm of ATAC vs. Faslodex pre- and post-op, what about that idea?

DR. BAUM: Yes, it is still very much on the table. I would love to do that. Faslodex is a very interesting molecule it's an estrogen receptor down regulator, so it has a unique mechanism of action. It also has anti-angiogenic properties, so I think two by two-factorial trial of aromatase vs. Faslodex pre-op vs. adjuvant. I think that would be a lovely study, biologically fascinating. At a workshop I was talking at last night, the one point I was making was that any future trials have to have a serious sound biological rationale, the idea of why not do three years of this and two years of that and cross over here and cross over there. These trials with different durations are so empirical, there is no biological underpinning for them. So, rather than looking at duration trials, I would like trials that have a biological underpinning.

DR. LOVE: In terms of treating a patient for adjuvant therapy off protocol right now, do you think that if an aromatase inhibitor is going to be used it ought to be anastrozole or do you think that letrozole or exemestane would be legitimately substituted.

DR. BAUM: Well, I so far resisted getting into a turf war here. Is this a class affect? I truly don't know. I can only speak for anastrozole in the ATAC trial. There are subtle differences in pharmacology and pharmacokinetics between the two non-steroidal aromatase inhibitors and even more so with the steroidal aromatase inhibitor exemestane, that could in theory lead to different results. I suspect that to a greater extent they will have the same efficacy, but I don't think you can assume that they will have the same trade off in adverse events.

DR. LOVE: Anything else you would like to add to anything you have said so far?

DR. BAUM: If I could be allowed a rhetorical flourish to end with. When I started in this game 25 years ago, it was us and them. The Americans banging on about chemotherapy, the Brits banging on about endocrine therapy. As the years go past we've come closer and closer together. One of the wonderful things about ATAC is that it is a warm and friendly collaboration between American investigators and European investigators. It comes at a time when American and Brits are standing shoulder to shoulder in the war against terrorism. We're also on the same side in the war against breast cancer.

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