Dr Conlin on Targeting CNS Metastases in the Treatment of Breast Cancer

Alison K. Conlin, MD, medical oncologist, Providence Cancer Institute Franz Clinic, discusses the importance of targeting central nervous system (CNS) metastases in the treatment of patients with breast cancer, highlighting ongoing treatment investigations for this population.

Over the past 5 years, there has been significant progress in the treatment paradigm for patients with HER2-positive breast cancer with CNS metastases, particularly since the phase 2 HER2CLIMB study (NCT02614794) demonstrated the efficacy of tucatinib (Tukysa) in this population, Conlin begins. This efficacy was specifically noted in patients with untreated or progressive disease, he states. Recent data from a pooled analysis of the phase 2 DESTINY-Breast01 (NCT03248492), phase 3 DESTINY-Breast02 (NCT03523585), and phase 3 DESTINY-Breast03 (NCT03529110) trials presented at the 2023 ESMO Congress showed that fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) elicited an ORR of 45.2% in patients with treated or stable CNS metastases and an ORR of 45.5% in those with untreated or active CNS metastases Conlin explains. Although the presentation involved pooled data and lacked a randomized prospective study design, the results were notably impressive, she adds. These findings indicate that there are viable options for effectively controlling untreated CNS disease in patients with HER2-positive breast cancer, expanding the choices available for their treatment, Conlin says.

The evolving understanding of HER2-positive breast cancer with CNS metastases is prompting a reassessment of available treatment strategies, she continues. Notably, insights from the phase 3 KATHERINE study (NCT01772472) have highlighted that although patients with high-risk HER2-positive disease experience improved outcomes with ado-trastuzumab emtansine (Kadcyla; T-DM1) vs trastuzumab, they still experience CNS recurrence rates comparable withthose experienced by patients who receive trastuzumab if they don't achieve a pathologic complete response to T-DM1, Conlin emphasizes. As the oncology field recognizes the CNS as a site where disease recurrences can occur, research focuses are shifting toward exploring preventive measures, she elucidates.

Ongoing National Cancer Institute–sponsored research is investigating the potential of using an oral TKI, such as tucatinib, to prevent CNS disease in patients deemed cured of their breast cancer, Conlin expands. Existing data support the use of neratinib (Nerlynx), another oral TKI,for the prevention of secondary CNS disease, she explains. The phase 2 BRIDGET study (NCT05323955) is actively examining the feasibility of treating isolated CNS recurrence with local therapy and exploring the addition of a TKI to trastuzumab plus pertuzumab or T-DM1 to prevent future CNS metastases or overall disease progression, Conlin adds. This trial’sperspective underscores the evolving view of the CNS as a distinct consideration, not only as a potential separate entity but also as an integral part of overall systemic disease control strategies, she concludes.