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Pertuzumab and trastuzumab plus chemotherapy for the treatment of HER2-positive metastatic breast cancer improved median overall survival (OS) by 15.7 months over standard first-line therapy
Sandra M. Swain, MD
Pertuzumab and trastuzumab plus chemotherapy for the treatment of HER2-positive metastatic breast cancer improved median overall survival (OS) by 15.7 months over standard first-line therapy, according to data from the CLEOPATRA study.
To gain further insight into these results, OncLive interviewed Sandra M. Swain, MD, Medical Director of the Washington Cancer Institute at MedStar Washington Hospital Center. Swain was the lead author on the study and presented the data at the 2014 ESMO Congress.
Could you provide some background on the CLEOPATRA trial?
CLEOPATRA is a placebo-controlled study in first-line treatment of metastatic breast cancer. What’s being studied is a combination of trastuzumab and pertuzumab with docetaxel versus trastuzumab, placebo, and docetaxel. In the preclinical setting, the combination of the two monoclonal antibodies had much more activity in treating tumors. In a human study published in the Journal of Clinical Oncology, it was seen that those patients who received pertuzumab alone after trastuzumab did not respond as well but when trastuzumab was added to pertuzumab, the response was higher. There are other data in the neoadjuvant setting suggesting both monoclonal antibodies are needed for optimal activity.
What was seen in this final overall survival analysis?
The data I presented at the 2014 ESMO meeting showed a median increase in overall survival of 15.7 months. It’s an amazing result. We had not reported the median overall survival data before; it hadn’t been reached for the pertuzumab arm and now it has been reached. The arm that received trastuzumab also had a very good survival of about 40 months. An improvement of 15.7 months is just remarkable.
This means that women are going to live a lot longer. In my personal experience, these monoclonal antibodies have changed the trajectory of HER2-positive disease — Women can now live fairly normal lives. Years ago, before we had these therapies, these patients died pretty quickly. This is amazing that now we can show such a survival benefit.
What does a community oncologist need to know about this analysis?
I think the standard first-line treatment for any patient with HER2-positive metastatic breast cancer should be pertuzumab, trastuzumab, and a taxane. Docetaxel was used in this study, though there’s been another study reported by Dr. Dang at Memorial Sloan Kettering Cancer Center using paclitaxel. I think, in practice, many community oncologists could use paclitaxel instead of docetaxel, though that was not in this study. As a practical matter, that’s what a lot of oncologists are doing.
Do you think the choice of chemotherapy could have a great effect or not?
We know that taxanes are synergistic. The choice of taxane probably does not make a difference but it hasn’t been tested — that is pertuzumab and trastuzumab has not been tested in the first-line with other chemotherapy agents.
What other questions need to be answered in this space?
I think there are a lot of questions that need to be answered. One question is: Do patients with ER-positive, HER2-positive breast cancer need chemotherapy or can they just receive the monoclonal antibodies and hormonal therapy? A study called PERTAIN is trying to answer that question. In this study, oncologists can choose whether to give chemotherapy or not but then the randomization is with hormonal therapy and trastuzumab or hormonal therapy, trastuzumab, and pertuzumab.
Another question is: If a patient hasn’t had previous pertuzumab in the first-line, can they get it second-line or later? There’s minimal data on this topic. There’s some phase II data showing activity. There is also a trial ongoing, the PHEREXA trial, looking at capecitabine with or without pertuzumab and trastuzumab — to see if activity can still be achieved in the later line.
Some issues still need to be resolved regarding toxicity, too. With the combination of pertuzumab and trastuzumab, there’s an increase in diarrhea. The current recommendation is that patients be given a prescription for loperamide and begin using it if they start having diarrhea. Diarrhea can be managed very well unless in severe cases. In severe cases, an oncologist might have to stop the taxane and continue the monoclonal antibodies to control a patient’s diarrhea. One very important aspect to note about toxicity is that the cardiac toxicity was not increased at all with the combination. Monitoring toxicity of this combination of agents is really important.