Select Excerpts from the Discussion

CD 2, Track 14

DR LOVE: Cliff, can you comment on the updated results from the HERA trial that were presented at ASCO 2006 by Ian Smith?

DR HUDIS: I was struck that the hazard for recurrence actually “blipped” upward after the year of trastuzumab ended (Smith 2006). I believe that leaves the door wide open that prolonged treatment may be better than stopping after one year.

Many were excited because of the FinHer data, which demonstrated that nine weeks of trastuzumab significantly lowered the risk of recurrence or death ( Joensuu 2006). I’m not disputing that result. However, we don’t have the data for two years versus one year of trastuzumab, and the hazard for recurrence went up at the end of the first year when trastuzumab was stopped. It may not turn out to be anything, but I thought it was provocative. That was the most interesting slide Ian Smith showed.

CD 2, Track 17

DR LOVE: Craig, do you think trastuzumab without chemotherapy has a role for the older, frail patient?

DR HENDERSON: I would be willing to consider it, but I certainly wouldn’t give it much credence. I believe the data on the synergy of trastuzumab and chemotherapy, both preclinical and clinical, are too compelling to spend much time on that for the vast majority of patients.

DR LOVE: Chuck, for an 82-year-old patient with an ER-negative, PR-negative, HER2-positive tumor, would you present the option of trastuzumab monotherapy?

DR GEYER: I don’t believe that’s unreasonable. Again, I would have to be convinced that chemotherapy was not indicated for that patient.

DR WOLFF: One way to avoid this problem for an elderly person, for whom you’re concerned about the potential for cardiac toxicity, might be to use a nonanthracycline regimen. You could use TCH, for which we have data (Slamon 2005).

Or, if you’re concerned about the toxicity associated with the higher doses of docetaxel, you may create a regimen. One I can think of is weekly paclitaxel for 12 weeks with trastuzumab, which is highly tolerable in most patients. You may be obtaining synergism from the chemotherapy/trastuzumab combination and avoiding the anthracycline cardiotoxicity, although we have no data for that.

DR CHLEBOWSKI: We tried to use TCH for an 83-year-old woman who had a 7-cm fungating lesion with palpable lymphadenopathy. She didn’t tolerate the chemotherapy, and we stopped it. Her tumor was shrinking, so we continued with three more cycles of trastuzumab.

At surgery, she showed a pathological complete response in the breast and lymph nodes. That’s the first time I’ve ever seen a patient with a fungating lesion have a pathological complete response.

DR LOVE: Joyce, have you used adjuvant trastuzumab as monotherapy?

DR O’SHAUGHNESSY: I usually try to sneak in a little low-dose weekly paclitaxel for patients with comorbidities. I saw a patient recently who was extremely elderly, and I was considering an aromatase inhibitor and trastuzumab alone for her.

CD 2, Track 18

DR GEYER: I must bring up Soon Paik’s data with cMYC, because the data are remarkable. The patients with coamplified tumors who receive chemotherapy alone do very poorly, whereas we’re still waiting for a recurrence after two years with the addition of trastuzumab. The separation of those curves and their plateaus suggest that something important is going on. Among the patients without cMYC amplification, we’re seeing the curves separate, but they look like typical chemotherapy curves in that we’re continuing to see recurrences even with trastuzumab (Kim 2005).

CD 2, Track 19

DR LOVE: Debu, is the TOPO II assay something that could be considered in clinical decision-making at this point?

DR TRIPATHY: We’ve known for years that TOPO II overexpression confers sensitivity to anthracyclines. This has been shown in cell-line models dating back 10 to 15 years. Now we see that TOPO II amplification seems to predict a better response to anthracyclines, and the lack of TOPO II amplification might mean that anthracyclines are not as important (Slamon 2005; Press 2005).

TOPO II is carrying more weight now. I would like to see the results from BCIRG 006 replicated in data sets from HERA and the NSABP and Intergroup studies. That should be imminently doable, and from what I understand, plans are underway.

My guess is that TOPO II amplification will end up being significant. I don’t believe it’s the only factor, but I do believe that it will enter into clinical utility.

I expect cases will arise in which we want to withhold an anthracycline and maybe use a taxane and trastuzumab. It’s not ready for prime time use, but it should be soon.

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