Post-Conference Perspectives: Updates in HER2+ Metastatic Breast Cancer; ASCO 2023 Highlights - Episode 5

HER2CLIMB-02: Tucatinib and T-DM1 in HER2+ Breast Cancer

Megan Kruse, MD, discusses the HER2CLIMB-02 study and the impact it may have on the HER2+ metastatic breast cancer treatment landscape.

Transcript:

Megan Kruse, MD: The HER2CLIMB-02 study is a study in progress that will look at the combination of trastuzumab emtansine with either placebo or tucatinib for patients with metastatic HER2 [human epidermal growth factor receptor 2]–positive breast cancer who have previously received treatment with a taxane and trastuzumab. The idea behind this study is to see if we can improve on our treatment in the second-line setting to determine if there’s any synergy between the combination of T-DM1 [trastuzumab emtansine] with tucatinib.

The clinical situation behind this is CNS [central nervous system] control. We know from other studies with T-DM1 [trastuzumab emtansine] that when patients have disease progression or failure of treatment, 1 of the sites where this can happen is in the brain or CNS. When you add T-DM1 [trastuzumab emtansine] to tucatinib, the hope is that you’re getting better extracranial coverage but also intracranial coverage for micrometastatic disease that’s not known, compared with what you’d be getting with T-DM1 [trastuzumab emtansine] alone or in the trial T-DM1 [trastuzumab emtansine] plus placebo. If this trial is positive, it’s going to make our treatment selection and sequencing very challenging. In a good way, it would open another treatment option for patients. T-DM1 [trastuzumab emtansine] has taken a back seat to T-DXd [trastuzumab deruxtecan] in the second-line setting, based on the results of the DESTINY-Breast03 study.

We also have the tucatinib-based regimen: tucatinib with capecitabine and trastuzumab. That’s another option in the second- and third-line settings. If this HER2CLIMB-02 study is positive, then you’re bringing T-DM1 [trastuzumab emtansine] back and also having a combination regimen that includes tucatinib. It would make that space that’s already fuzzy a little fuzzier in terms of how we should sequence these agents. It leads to the biggest question in our field overall, and 1 of the hardest to answer, because sequencing trials are particularly difficult to accomplish.

Transcript edited for clarity.