Breast Cancer Update Live Think Tank 2008

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Optimizing First-Line Systemic Therapy for Patients with ER-Positive,
HER2-Positive Metastatic Disease

Tracks 26-27

DR LOVE: What do you think about the data from the TAnDEM trial, comparing anastrozole with or without trastuzumab for patients with HER2-positive, hormone receptor-positive breast cancer?

DR PEGRAM: The TAnDEM trial data support the hypothesis that cross-talk perturbation may be efficacious. It certainly met its primary endpoints in terms of demonstrating efficacy (2.3). However, it did not prove the hypothesis because the trial had no trastuzumab-alone control arm.

That’s the big question with regard to TAnDEM in terms of the science: Would it have demonstrated superiority over a trastuzumab-alone control arm? The result with trastuzumab and an aromatase inhibitor was not particularly impressive in this series, either.

2.3

DR LOVE: Joyce, how do you approach first-line therapy for a patient who has hormone receptor-positive, HER2-positive breast cancer, assuming she has received no prior anti-HER2 therapy?

DR O’SHAUGHNESSY: I usually administer endocrine therapy first, and some patients fare extremely well for a long time.

I go back to Kent Osborne’s paper in the Journal of the National Cancer Institute a few years ago, which reported retrospectively evaluating patients with HER2-positive versus HER2-negative disease with regard to tamoxifen benefit in the adjuvant setting based on ER-positive, PR-positive versus ER-positive, PR-negative status (Arpino 2005).

The patients with ER-positive, PR-positive, HER2-positive breast cancer did receive some benefit from tamoxifen in the adjuvant setting, so I believe it’s not an absolute that these patients will not receive some benefit, and I initially use endocrine therapy alone.

Combining Trastuzumab with Endocrine Therapy for Hormone Receptor-Positive, HER2-Positive Disease

DR LOVE: Dennis, what about the patient who received prior adjuvant trastuzumab? How do you approach that decision in terms of anti-HER2 therapy on relapse, and how do you factor in the time since the last trastuzumab administration?

DR SLAMON: If the patient has blown through a trastuzumab regimen and relapsed quickly, within a year after receiving adjuvant trastuzumab, I consider an alternative targeting agent, such as lapatinib.

If it’s been a year, 18 months or more, I consider using trastuzumab with another therapeutic agent — vinorelbine or gemcitabine. A number of agents can be used while still using trastuzumab.

First-Line Therapy for Patients Who Relapse After Receiving Adjuvant Trastuzumab