Targeted and endocrine therapy combination results in concordant, superior progression-free survival (PFS), suggesting similar mechanisms of targetable endocrine resistance between metastatic sites, according to a meta-analysis by researchers with the Albacete University Hospital in Spain presented on Saturday, December 10, during the San Antonio Breast Cancer Symposium

The group noted that metastatic sites are usually classified as visceral or nonvisceral in clinical studies, but this has little influence in treatment decisions, particularly in the absence of clinical urgency. As such, they conducted a meta-analysis of randomized controlled trials investigating three different anticancer strategies in metastatic breast cancer.

  • Comparison of two endocrine strategies
  • Endocrine therapy and targeted therapy compared with endocrine therapy alone
  • New human epidermal growth factor receptor 2 (HER2) targeted therapy compared with existing HER2 targeted therapy

Researchers found a significant difference in PFS between women with visceral versus nonvisceral metastases when two endocrine strategies were compared, with benefits limited to women with visceral metastases. Yet the combination of an endocrine therapy and a targeted therapy was associated with better PFS compared to endocrine therapy alone for both groups. Newer HER2 targeted therapies were associated with significantly better PFS only in visceral metastases. Finally, overall survival (OS) benefit with new HER2 therapies was observed only for women with visceral metastases.

The authors concluded, “Discordant responses with endocrine strategy alone support use of targeted therapy, rather than a change in endocrine agent at disease progression. New HER2 therapies display continued challenges of drug penetration to areas of limited vascularization (e.g., soft tissue, bone) with no PFS or OS benefit in that group despite impressive benefits in the overall population.”

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