Slides from a presentation at SABCS 2009 and transcribed comments from an interview with Mark D Pegram, MD (12/23/09)

DR PEGRAM: This was the third planned interim analysis of the BCIRG 006 trial. It is important to note that the study was not powered to compare TCH to
AC → TH. Any comparison between the two trastuzumab arms that one makes in this trial is unplanned and speculative.

There were two prior planned interim analyses that had been presented that demonstrated that both of the trastuzumab-containing arms were significantly superior to the nontrastuzumab control, which was anthracycline and taxane-based combination chemotherapy.

It appeared previously that there might have been a graphical trend in favor of the AC → TH arm compared to the TCH arm. However, when statistical tests have been applied comparing the two trastuzumab-containing arms, there is no statistical difference in the first two interim analyses. In this third planned interim analysis, there is again the graphical appearance that the anthracycline-containing arm is trending a little bit better. From a statistical point of view it is again impossible to discriminate fairly between the two trastuzumab-containing arms. Since the study was not powered for noninferiority, one cannot rule out the possibility that anthracycline-containing regimens might be slightly better. The absolute numbers of adverse events and deaths between the arms suggest that there could be some trends in favor of anthracyclines.

The BCIRG group made the supposition that anthracyclines would be more important in patients with lots of positive nodes, as opposed to those with node-negative disease. They performed that comparison and found that there was no difference in the group of patients with lots of nodes with regard to efficacy of AC → TH versus TCH. The notion that intrinsic risk might be a clinical factor that one could use to decide whether to use anthracyclines did not hold up.

DR LOVE: In general, have you been using TCH yourself off study?

DR PEGRAM: I have been. It is an efficacious regimen that does have a different spectrum of toxicities, and therefore it is a therapeutic consideration. If somebody came to me for a second opinion and the referring physician had recommended an AC followed by TH approach, I would not say that it was inappropriate. It might be entirely appropriate. But I would argue that it’s reasonable for patients to understand that both of these are treatment options that are available to them, and they can weigh in based on their understanding of the various toxicities.

DR LOVE: Are you generally continuing to use TCH as your preferred regimen?

DR PEGRAM: I am generally continuing to use TCH as my preferred regimen. TCH is a reasonable treatment option, but clearly there is this non-statistically significant trend in favor of the AC → TH arm. It suggests the possibility that there could be inferiority of TCH in an appropriately powered study, which has not been conducted. It remains an open question.

In the grand scheme of things, I believe history will record that quibbling over which chemotherapy backbone to use with trastuzumab is going to be irrelevant. We need to move on and the next question is: Can we do better than chemo/trastuzumab?

Dr Pegram is Full Professor of Medicine and Director for the Translational Research Program at the UM Sylvester Comprehensive Cancer Center’s Braman Family Breast Cancer Research Institute in Miami, Florida.