TCH versus ACTH

DR HUDIS: I have equipoise on the question of TCH right now. We have data that say that TCH beats ACT, with docetaxel, and we have data that say ACTH — pick your taxane — beats ACT. We don’t have direct data that show any significant difference between TCH versus other trastuzumab-containing regimens.

I will say that we have a greater weight of evidence for the anthracycline-containing regimens. Also, at least at the first analysis, there was a suggestion that some of the patients might benefit from the inclusion of the anthracycline.

I’m alluding to the TOPO II testing, which is not in general use right now but again raises the possibility that the omission of the anthracycline might be disadvantageous for some patients. That’s the long story.

The short story is that TCH is a reasonable option, and it’ll be even more reasonable when a peer-reviewed paper reports on it.

Breast Cancer Update: Cardiologic Issues in Breast Cancer Management 2007 (1)

DR BURSTEIN: In the preliminary work from the BCIRG 006 trial that Dennis Slamon and Mike Press reported at the San Antonio meeting in 2005, they suggested that in TOPO II overexpressors, the ACTH arm was superior to the nonanthracycline/trastuzumab (TCH) arm. For the majority of tumors in which the TOPO II is not amplified, however, TCH was more or less equivalent to ACTH.

If in the aggregate they’re the same, it washes out the effects of the TOPO II test question. I believe that if clinicians decide they can use a nonanthracycline/trastuzumab-based regimen, it doesn’t matter whether they perform the TOPO II testing.

For patients with TOPO II-nonamplified tumors, the trastuzumab-based arms are superior to the nontrastuzumab arm. Visually, you see less difference between the two trastuzumab-based arms than there seemed to be a year ago.

I wasn’t certain it was logical to test TOPO II to begin with because the data were preliminary with short follow-up and reflected subsets of patients in a three-arm study, which is always dodgy. At this point, I believe we have even less rationale for testing. I assume clinicians will either continue to use AC TH, because they’ll say that’s what they’ve always used and it’s effective, or they’ll increasingly switch to TCH. In either case, you don’t need TOPO II testing to help you.

Breast Cancer Update 2007 (3)

DR WINER: It is worth bearing in mind that these are subset analyses, and at our center we don’t perform TOPO II testing. In my view, this is not ready for prime time.

A year ago, the suggestion emerged from 006 that for those women with TOPO II amplification in addition to HER2 amplification, the anthracycline seemed to matter more. The women who received AC followed by docetaxel/trastuzumab and had TOPO II amplification had the best outcome, and the women who received TCH in the presence of TOPO II amplification didn’t do quite as well.

This year, Dr Slamon presented two findings. First, in general, women whose tumors were TOPO II and HER2 amplified seemed to have a better outcome than those whose tumors were not TOPO II amplified. Second, among those women whose tumors were TOPO II amplified, a difference didn’t seem to appear between TCH and ACTH. It is also worth pointing out that among those women whose tumors were TOPO II amplified, those who didn’t receive trastuzumab also did quite well.

Breast Cancer Update 2007 (3)

DR HOLMES: The idea behind the BCIRG 006 trial was to evaluate patients with centrally determined FISH-positive disease to establish whether up-front treatment with trastuzumab reduced relapse rate.

The second strategy was based on the understanding of the mechanisms of synergy and whether a nonanthracycline containing regimen could be evaluated, particularly because of the known cardiotoxicity of trastuzumab. Would it be possible to incorporate trastuzumab earlier without having to wait until the completion of the anthracycline?

The great thing about this trial is that it continues to provide new answers and new questions, and now we find that the TCH and ACTH arms are equally effective.

The issue of TOPO II status in selection of therapy for patients with HER2-positive disease remains an unanswered question. Some would say that if the disease is TOPO II amplified, then perhaps the patient should receive an anthracycline. Others would argue that you can avoid the cardiotoxicity, because you do not have to administer the anthracycline, and you can choose a much more user-friendly trastuzumab regimen.

I believe that many more of us will use the TCH regimen if we’re worried about cardiac toxicity.

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