First line treatment against metastatic breast cancer
Dr Karen Gelmon – BC Cancer Agency, Vancouver, Canada
Professor Gelmon, you’ve been talking about a head-to-head comparison of two HER2 blocking agents. Trastuzumab, of course, has done a lot in metastatic breast cancer, you’ve been trying lapatinib, what is it that you were doing in this study?
Lapatinib has been approved in combination with capecitabine for patients who have had prior Herceptin and there has been a lot of work looking at lapatinib with other cytotoxics, including paclitaxel, there was a big study in China looking at that. We felt a number of years ago that it was very important to do a head-to-head comparison of lapatinib plus taxane versus Herceptin plus taxane in first line metastatic HER2 positive breast cancer.
But trastuzumab and lapatinib do the same thing except lapatinib does an extra one as well, doesn’t it?
It’s a question if they do the same thing. Certainly they’re both anti-HER2 agents, lapatinib targets HER1, EGFR and HER2. It’s an oral agent, it goes across membranes, its activity is different. Trastuzumab just targets HER2; trastuzumab was out of the gate first, was the first one approved but lapatinib certainly has been an effective agent. But we wanted to compare them, we felt it was important to compare them, so clinicians, when they looked at their patient with first line metastatic disease, could make a rational choice of which agent to use.
And of course it’s nice to have the choice, isn’t it? So you had around 500 patients, what happened?
It’s an international study done around the world, multi-centre study. It was run by the NCIC, the National Cancer Institute of Canada, and with GSK’s help. Basically we needed to enrol 536 HER2 positively centrally confirmed patients; we enrolled over 600 to get that number. This was an interim analysis that I presented but it showed that the progression free survival, so the time from enrolment to progression, was significantly longer for those patients who got trastuzumab compared to lapatinib.
By how much?
When we looked at the whole population it was 2.6 months different but when we looked at just those women who had HER2 centrally confirmed it was 4.7 months. That’s a long time for a woman with metastatic breast cancer so that’s very statistically significant.
So lapatinib is still recommended for Herceptin refractory patients but what about first line?
That’s a very good question. In our study people could have had Herceptin in the adjuvant setting, only 18% of people had it, but they had to have had it more than a year before. So that’s a group that’s probably not refractory. Lapatinib certainly after Herceptin in the metastatic setting is an active agent, as shown by the previous trials. It may be that in patients who progress on adjuvant Herceptin lapatinib would be a good choice. One of the important things about this study is we’ve got tissue on all of the patients to check their HER2 so we’re going to be doing studies on those tissues to see. It may be we’ll define a group of patients who would really do better with lapatinib but overall right now it looks like Herceptin is the more active agent.
It seems a very firm result, what are your clinical recommendations to pass on?
My clinical recommendations are that for a woman coming with either de novo, newly diagnosed, HER2 positive metastatic disease or a woman who had adjuvant treatment and now is getting Herceptin, that on the basis of these results I would think about Herceptin first, or one of the newer agents maybe. I think lapatinib has a role and we don’t know its role in the refractory patients or in second or third line in combination with capecitabine but for first line I would recommend trastuzumab based on the results of this trial.
Karen, thank you very much indeed.