Video
The Current Standard-of-Care for Patients with HER2+ Metastatic Breast Cancer
Author(s):
Neil M. Iyengar, MD briefly reviews the standard-of-care first-line treatment for patients with metastatic HER2+ breast cancer as well as historical approaches to progression after first-line treatment.
Neil M. Iyengar, MD: In the first line setting for HER2 positive metastatic breast cancer, the seminal CLEOPATRA trial has of course established the standard of care with taxane plus dual antibody HER2 directed therapy with trastuzumab and pertuzumab. We have long term follow up data from CLEOPATRA, which shows an overall survival benefit at eight years of follow up. In fact, we know that median overall survival is one and a half years longer in the pertuzumab containing arm, with a median OS of about five years. However, at eight years, the overall survival rate was about 37%. So there really is much room for improvement here.
Are there situations where I might not use the CLEOPATRA regimen in the first line. There are some situations where patients may have contraindications to chemotherapy or have a poor functional status, which really limits the use of chemotherapy or increases the risk of chemotherapy. And we do have data for those patients who are also hormone receptor positive that we can combine endocrine therapy with antibody therapy. For example, in the phase two PERTAIN trial, the combination of an aromatase inhibitor with Herceptin and pertuzumab had a 1.5-year median progression free survival. In other patient populations, there are some instances where I may not use the ClEOPATRA based regimen. For example, some patients can present with brain metastases even as early as the first line setting. For example, we know from the adjuvant KATHERINE study that about five percent of patients in each arm presented with brain metastasis as their first site of recurrence. And there are newer agents, of course, that have CNS activity where I might actually consider using them as early as the first line setting.
Our historic standard in the second line setting for HER2 positive metastatic breast cancer has of course been trastuzumab emtansine or T-DM1 based on data from the phase three EMILIA study. In that study, we saw a benefit of T-DM1 in terms of both progression free survival and overall survival. But of course, now we have newer agents that are available to us in the second line setting or beyond, that have been compared to T-DM1, with new standards of care being established.
