KAMILLA Data Reinforce Favorable Benefit/Risk Profile of T-DM1 in HER2+ Breast Cancer

Rachel Wuerstlein, MD, discusses the safety and the efficacy observed with ado-trastuzumab emtansine in patients with HER2-positive breast cancer and the next steps for research with the agent.

Data from the phase 3 KAMILLA trial (NCT01702571) confirm the safety and efficacy of ado-trastuzumab emtansine (T-DM1, Kadcyla) that had previously been observed in patients with previously treated HER2-positive breast cancer, according to Rachel Wuerstlein, MD, who added that no new safety signals were observed.

Results from the study, which were presented during the 2021 ASCO Annual Meeting, showed that safety and efficacy findings with the agent were generally similar between a global cohort of patients (n = 2002) and an Asia cohort (n = 181). Although the rate of grade 3 or higher thrombocytopenia was higher in the Asia cohort vs the global cohort, at 36.5% vs 3.7%, respectively, most of these effects fully resolved.1

At the time of the data cutoff, the median progression-free survival (PFS) in the global and Asia cohorts was 6.8 months (95% CI, 5.8-7.6) and 5.7 months (95% CI, 5.5-7.0), respectively. The median overall survival (OS) between the cohorts was also found to be similar, at 27.2 months (95% CI, 25.5-28.7) and 29.5 months (95% CI, 21.1–non-estimable), respectively. Notably, however, the median PFS and OS in both cohorts was found to decrease with increasing lines of previous therapy.

“It was concluded that [this trial provided additional] relevant information, with no new signals reported in comparison with previous publications of T-DM1; this is important, as this [agent] is now the [global] standard of care in the second line and [beyond] in [patients with] HER2-positive metastatic breast cancer,” Wuerstlein said. “More and more interesting data are coming out [that will shed additional light] on this agent.”

In an interview with OncLive®, Wuerstlein, of the Unïversität Müchen, further discussed the safety and efficacy observed with T-DM1 in patients with HER2-positive breast cancer and the next steps for research with the agent.

OncLive®: What was the rationale for the phase 3 KAMILLA trial with trastuzumab emtansine in patients with HER2-positive breast cancer?

Wuerstein: KAMILLA was a trial [that evaluated] the safety and efficacy [of T-DM1 in] a global and Asian cohort. [The research] was of high importance because [we needed] more safety data for T-DM1 in metastatic breast cancer at the time, after [data from] the pivotal phase 3 EMILIA [NCT00829166] and TH3RESA [NCT00829166] trials were published. KAMILLA [has enrolled] the highest number of patients [to date] for [a trial examining] T-DM1, with more than 2000 patients in the global cohort and 181 patients in the Asian cohort.

What were the key safety differences observed between the global cohort and the Asian cohort?

Interestingly, we [knew] from the previous trials that some differences exist, mainly [with regard to] safety with T-DM1, between the global cohort and Asian cohorts. What we did find in KAMILLA, and this is why we also [added an] Asian cohort, is a high rate of thrombocytopenia, which was a chosen end point.

When looking at the numbers, [we saw] a difference in thrombocytopenia [between the cohorts]; the effect [was reported in] 8.7% [of those] in the global cohort and 27.1% [of those] in the Asian cohort. Grade 3 [or higher] thrombocytopenia was [experienced by] 3.7% [of those] in the global cohort and 36.5% [of those] in the Asian cohort. Importantly, all these cases could be resolved [with a] dose reduction and patients could remain on [the drug]. Dose reductions were made in 22.5% of those in the global cohort and 60.2% of those in the Asian cohort. We [also saw] a low rate of [discontinuation].

Importantly, what fortunately did not see a higher rate of bleeding complications due to thrombocytopenia. [However,] there is a relevant difference [with regard to] thrombocytopenia [in these cohorts], and we think this might be [because of] different genetic polymorphisms between [the] global population and the Asian population. No relevant new safety signals [were observed.]

What were the efficacy data in these cohorts?

[Data regarding] PFS and OS were [similar in the cohorts]. Importantly, OS was higher for the Asian population after follow-up. KAMILLA again proved that the earlier we use T-DM1 in HER2-positive metastatic breast cancer, the more effective it is. [Median PFS and OS decreased with increasing lines of prior therapy.]

As already published, important data [have come] from KAMILLA with regard to brain metastases. T-DM1 [has been shown to be] highly effective and safe in [patients with] brain metastases. Thus, [the agent] broadens our range of treatment options in not only metastatic [disease], but also to [patients with] metastatic HER2-positive breast cancer who have brain metastases.

What are the clinical implications of this research?

KAMILLA [confirms] important data with T-DM1 that we saw from previous trials [that had enrolled] smaller numbers of patients] with metastatic breast cancer. One key result is that we did not find any new safety signals. If you look at secondary end points of KAMILLA, there has been a variety of adverse effects of special interest. For example, with regard to pneumonitis, we did not find any new signal; this is confirmation of what we knew before. This plays an important role because T-DM1 is not only used in metastatic breast cancer, but it's been moving to post-neoadjuvant treatment [setting for patients with] early breast cancer.

The confirmation of the efficacy data is also important because [provides another piece to the] puzzle of new information we get [with emerging] treatment options; it also [sheds some light with regard to] sequencing treatment in metastatic HER2-positive breast cancer.

What are the next steps for research with T-DM1?

This is an interesting question to consider. T-DM1 is a well-described drug in metastatic breast cancer [for use in the] second-line or [later setting], but also in the post-neoadjuvant [setting]. My [research team has] been working on this question. It's now time to move [this drug] to the neoadjuvant setting.


  1. Wuerstlein R, Ellis P, Montemurro F, et al. Safety of trastuzumab emtansine (T-DM1) in patients (pts) with HER2-positive locally advanced or metastatic breast cancer (mBC): final results from KAMILLA cohorts 1 (global) and 2 (Asia). J Clin Oncol. 2021;39(suppl 15):1039. doi:10.1200/JCO.2021.39.15_suppl.1039