Differences Between the Global and Asian HER2+ BC Cohorts in the KAMILLA Trial

Rachel Wuerstein, MD, of the Unïversität Müchen, discusses the differences between the global and Asian cohorts in the KAMILLA trial (NCT01702571), which evaluates the benefit of trastuzumab emtansine (T-DM1, Kadcyla) in patients with HER2-positive breast cancer who have received prior anti-HER2 and chemotherapy-based treatment.

According to Wuerstein, there are several differences between the global and the Asian cohorts in the KAMILLA trial. One such difference is the rate of thrombocytopenia, which occurred in 8.7% of the global cohort and 27% in the Asian cohort. Additionally, grade 3 thrombocytopenia occurred in 36% of cases in the Asian cohort and 3.7% of the cases in the global cohort. All cases of thrombocytopenia could be resolved by dose reductions, according to Wuerstein, keeping patients on track.

There as a low rate of trial discontinuations for both cohorts. However, dose reductions occurred in 22% of the global cohort and 60% of the Asian cohort. However, there was not a higher rate of bleeding complications due to thrombocytopenia in the Asian cohort. According to Wuerstein, this may be due to the different genetic polymorphisms between the global and Asian populations.

0:08 | Interestingly, what we did know from the previous trials, there are some differences in safety of some of the tracks so far in T-DM1 between the global cohort and Asian cohort. What we did find in KAMILLA, and therefore we also entered in the Asian cohort, is a higher rate of thrombocytopenia. Thrombocytopenia was 1 chosen end point in the KAMILLA trial. So, what we did see in numbers is a difference in thrombocytopenia general adverse events of 8.7% in the global cohort, 27% in the Asian cohort, and for grade 3 thrombocytopenia, it was 3.7% in the global cohort and 36% in the Asian cohort again. Importantly, all these cases could be resolved by dose reduction and patients could remain on the track.

We had a low rate of trial (discontinuation) for those patients or dropouts, but equivalently, a difference in dose reductions of global 22% and in the Asian cohort 60%. What we did not see, fortunately, was a higher rate of bleeding complications due to thrombocytopenia. So yes, there is an effect and relevant difference in the adverse effect event of thrombocytopenia, and we think the rationale for this might be different genetic polymorphisms between global populations and Asian populations by itself. As I already said, there was no relevant new safety signal, just the difference in the population [sizes], but no difference in maintenance of the trial.