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Track 5

DR LOVE: Cliff, can you discuss the German trial that evaluated the continuation of trastuzumab upon disease progression?

DR HUDIS: Von Minckwitz reported the results at ASCO 2008. The trial was closed early when lapatinib became available in Germany. Upon disease progression, patients were switched to capecitabine and were randomly assigned to either continue or discontinue trastuzumab (Von Minckwitz 2008). It’s precisely similar to Charlie Geyer’s lapatinib study (Geyer 2006), except it’s with trastuzumab.

The shock to many of us was the near doubling of the overall response rate and the approximately 50 percent improvement in progression-free survival associated with the continuation of trastuzumab. The trial was underpowered because it was closed prematurely, but it’s still the largest experience we have (Von Minckwitz 2008; [5.1]).

DR LOVE: What do you think we would have seen if the trial had included a third arm with lapatinib?

DR HUDIS: My prediction, based on these data, is that the efficacy would have been equivalent — but I don’t know. This trial preselected a cohort of patients who tolerated trastuzumab. Some gastrointestinal and skin toxicities are associated with lapatinib, so I believe, by comparison, lapatinib would appear worse.

DR LOVE: Julie, can you discuss the trial evaluating the combination of lapatinib and trastuzumab that was presented by Joyce O’Shaughnessy at ASCO 2008?

DR GRALOW: Joyce presented a trial in which upon disease progression while receiving trastuzumab, patients went on to receive either single-agent lapatinib or lapatinib with the continuation of trastuzumab.

An advantage was demonstrated with the combination for these patients who had received a considerable amount of prior trastuzumab (O’Shaughnessy 2008; [5.2]).

Admittedly, the patients were heavily pretreated and in neither arm did they have a long time before their disease progressed again. They didn’t receive any chemotherapy with these drugs (O’Shaughnessy 2008).

So it might be that the combination of lapatinib and trastuzumab is better than either alone, but the addition of some chemotherapy is even superior.

DR LOVE: Cliff, what are some of the new anti-HER2 strategies being tested in clinical trials?

DR HUDIS: In patients with trastuzumab-refractory breast cancer, three classes of drugs have above a 20 percent response rate when combined with trastuzumab: TDM1 (trastuzumab with maytansine), pertuzumab and HSP90 inhibitors.

DR LOVE: John, what is your thinking with regard to this patient?

PROF CROWN: I would go back and treat her the way we would treat a patient with de novo HER2-positive metastatic disease, with a taxane/trastuzumab regimen — either docetaxel/trastuzumab or docetaxel/carboplatin/trastuzumab.

She would have a reasonable chance of responding to one of those regimens, and it might re-establish control of her disease.

DR LOVE: Julie, what about continuing trastuzumab and switching to another chemotherapy?

DR GRALOW: I believe that’s on the table too. For this particular patient, we know that she had tried lapatinib, didn’t fare well and refused to ever take it again. So that’s off the table.

I do believe we have data indicating that capecitabine with the continuation of trastuzumab is better than capecitabine alone (Von Minckwitz 2008; [5.1]). We don’t, however, have a head-to-head comparison with capecitabine/lapatinib.