Dr Peter Kaufman discusses the results phase III clinical trial comparing eribulin mesylate with the capecitabine for patients with locally advanced or metastatic breast cancer. The study failed to demonstrate a significant difference between the two arms, however there was a numerical trend favouring eribulin. Dr Kaufman concludes by suggesting that eribulin may in fact be superior within certain patient sub-groups, but further studies are required to establish this.
Press conference coverage here.
The 2012 CTRC-AACR San Antonio Breast Cancer Symposium, 4-8 December
Eribulin fails to demonstrate superiority over capecitabine in advanced breast cancer
Dr Peter Kaufman – Norris-Cotton Cancer Center, Lebanon, USA
The study I’ll be presenting is a large international phase III randomised trial of eribulin versus capecitabine in women with metastatic breast cancer in the first, second and third line setting. So this is the first data evaluating eribulin earlier in the course of metastatic breast cancer. The rationale for our study largely is simply that eribulin, as is well known to many of us, found in the EMBRACE trial to have an overall survival benefit in women with heavily pre-treated breast cancer, so in fact it’s the first cytotoxic agent to have survival benefit in women with heavily pre-treated metastatic breast cancer. Capecitabine is a fairly widely used therapy worldwide in the first, second and third line and the goal of our study was to compare eribulin to Xeloda earlier in the course of metastatic disease. So the study was designed as a superiority trial. It’s a simple, straightforward phase III study with a one to one randomisation, women being randomised one to one fashion to receive either eribulin, conventional dose and schedule, so eribulin mesylate was given at 1.4mg/m2 day one and eight, cue three weeks, versus a conventional dose of capecitabine.
The study enrolled approximately 1,100 patients in total so it’s certainly a large trial. The findings are interesting, we did not demonstrate a statistically significant superiority of eribulin over capecitabine, however there was a trend favouring eribulin that is interesting. The median overall survival for patients receiving eribulin is 15.9 months versus 14.5 months median OS for those receiving capecitabine. So, again, this difference is not statistically significant but there’s a numerical trend favouring eribulin. If you look at the survival curves, the Kaplan-Meier plots, the curves in fact separate early and remain separate throughout the course of the study, which is interesting as well. As well we did not meet our primary objective which was to demonstrate eribulin to be superior to Xeloda; it compared favourably and this really is fair to say it’s the first study demonstrating activity of eribulin earlier in the course of metastatic breast cancer, again specifically in the first, second and third line setting. Our conclusion is that eribulin overall has reasonably comparable activity to capecitabine, pointing out that this is not a non-inferiority trial so it’s not statistically demonstrating equivalency by any means. But with a study of this size, certainly I feel it demonstrates activity of eribulin in this patient population and activity that compares quite favourably to a widely used standard of care.
So specifically we had several pre-planned exploratory subgroup analyses included in the study plan, the statistical plan, and those findings, in fact, were quite interesting. In the triple negative breast cancer patient population we saw a significantly superior trend favouring eribulin and the size of the triple negative population was reasonable in this study, approximately 25% of patients overall in the study had triple negative breast cancer. So the total number of triple negative patients was 284 and in that group there, in fact, is a five month numerical difference in the median overall survival between eribulin and capecitabine favouring eribulin. So there was a five month numerical difference with a hazard ratio of approximately 0.7. So that’s a subgroup that potentially might have a greater therapeutic benefit from eribulin, although that’s not proven, I would emphasise, on the basis of this study but it’s an interesting finding. In the ER negative subset as well as the HER2 negative subset had trends that were somewhat better than the hazard ratio, trends favouring eribulin compared to capecitabine that were somewhat numerically better than the hazard ratio for the overall population. The hazard ratio for the overall study for overall survival was 0.879 favouring eribulin, but again not statistically significant.
Are there plans to look at the subgroups again?
We’re actively discussing and considering further work, certainly. I and a number of my co-investigators are intrigued by the finding I just mentioned in the triple negative population so we’re performing some further analyses, I should say, but we’re actively considering and discussing further studies in the triple negative population.