Mothaffar F. Rimawi, MD, associate professor and director of clinical research at the Lester and Sue Smith Breast Center at Baylor College of Medicine, discusses the role of TKIs in the treatment of HER2-positive breast cancer.
Mothaffar F. Rimawi, MD, associate professor and director of clinical research at the Lester and Sue Smith Breast Center at Baylor College of Medicine, discusses the role of TKIs in the treatment of patients with HER2-positive breast cancer.
Many patients develop resistance to the HER2-targeted antibodies trastuzumab (Herceptin) and pertuzumab (Perjeta), and researchers need to figure out strategies to continue prolonging survival. The TKIs neratinib (Nerlynx) and tucatinib could have potential here, says Rimawi. Neratinib is indicated in the extended adjuvant setting, but not yet in the metastatic setting.
There is an ongoing phase III study that is comparing the use of neratinib in combination with capecitabine with the use of lapatinib (Tykerb), another HER2 TKI, plus capecitabine. Although the neratinib combination regimen seems poised to have a role in the third line, Rimawi notes that it could be moved earlier in treatment.
A non-randomized phase II study is also evaluating the safety and efficacy of the combination of the TKI tucatinib and trastuzumab with capecitabine for the treatment of leptomeningeal metastases in patients with HER2-positive cancer, he adds, with results likely to read out in the next year or 2.
Additionally, there is a lot of attention being paid to these agents for their effect on central nervous system (CNS) metastases. This is a major challenge in HER2-positive breast cancer, Rimawi explains, as approximately half of these patients will develop CNS progression.