Experts share brief insights on novel agents in development for HER2+ breast cancer and consider how they may impact the treatment landscape.
Sara Tolaney, MD:In this case, we used T-DXd [trastuzumab deruxtecan] in someone with active brain metastases. Nancy, you’re very involved in developing novel purchases for treating people with active CNS [central nervous system] disease. Are there particular drugs you’re excited about or things that you are investigating in this space?
Nancy Lin, MD: Together with my collaborator Jean Zhao, we’ve been investigating a number of combinations in precritical models of breast cancer brain metastases, prioritizing which combinations or drugs to take into the clinic. An example of that is a drug called GDC-0084, which is a dual PI3 kinase mTOR inhibitor that’s blood-brain-barrier permeable. There’s a phase 2 trial ongoing that combines GDC-0084 with trastuzumab to see if the clinical data would replicate the preclinical data, which looks promising. Other examples include a number of additional HER2 [human epidermal growth factor receptor 2] TKIs [tyrosine kinase inhibitors], so we go along that route as well. Other ways to refine HER2 TKIs include increasing the amount of blood-brain barrier, penetration across an intact blood-brain barrier, or different amounts of inhibition of EGFR vs HER2 with different strengths of inhibition.
One of the drugs, from Zion [Pharma], is ZN-A-1041, which is a blood-brain-permeable HER2 TKI. It’s being looked at in combination with HP [trastuzumab pertuzumab] during the HP [trastuzumab pertuzumab] maintenance part of therapy. That could eventually be an interesting approach to look at, to see if it could prevent brain metastases. The other combination, which is being looked at, is with T-DXd [trastuzumab deruxtecan]. In China, there is a novel HER2 TKI, pyrotinib, which is through phase 3 trials and is available there. It’s not available in the United States, but from a global standpoint, having more than 1 HER2 TKI to choose from and the potential price pressures may be useful. The compound has been shown to work extracranially and in the CNS. There was a CNS-specific trial that has a high response rate in relatively treatment-naïve patients compared with what we typically see in the United States in our metastatic population.
Sara Tolaney, MD:It’s nice to hear that there are lots of other things coming along. That’s great.
Transcript edited for clarity.