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A Review of the Efficacy of Tyrosine Kinase Inhibitors in the Treatment of Patients with HER2-Positive Breast Cancer with or without Brain Metastases

Conference Correspondent

Brain metastases affect up to 50% of patients with HER2-positive metastatic breast cancer and is linked to a high death rate.1 Patients with brain metastases treatment outcomes are influenced by the treatment activity in the central nervous system.1 Tyrosine kinase inhibitor (TKI)-based regimens are now being used in the treatment of patients with HER2-positive metastatic breast cancer.1 The goal of this systematic review was to compare the clinical outcomes of patients with or without brain metastases who were treated with TKI-containing versus non–TKI-containing therapies.1

The study included a thorough literature search of PubMed, EMBASE, CENTRAL, and oncology conference proceedings to find randomized clinical trials analyzing systemic therapies with anti-HER2 TKI-containing treatments and non–TKI-containing treatments in patients with HER2-positive metastatic breast cancer.1 Data on progression-free survival (PFS) and overall survival in subgroups of patients with and without brain metastases at baseline were screened for in the studies.1

Five randomized controlled trials with a total of 2437 patients were included among the 1671 records found.1 A total of 490 patients had brain metastases and 1947 patients had no brain metastases at baseline.1 Tucatinib, lapatinib, pyrotinib, or afatinib in combination with cytotoxic chemotherapy trastuzumab were used in the intervention arm. Cytotoxic chemotherapy trastuzumab or trastuzumab emtansine were used in the control arm.1 There was no trial of neratinib that met the inclusion criteria.1 Patients with stable and asymptomatic brain metastases were permitted in the trials, with the exception of one study (HER2CLIMB), which included patients with progressing untreated brain metastases.1 The majority (92.8%) of patients had previously received trastuzumab treatment.1 In terms of PFS, both patients with and without brain metastases showed a nonstatistically significant trend favoring TKI-containing treatments.1

TKI-containing treatments improved PFS in all patients, regardless of brain metastases status.1 After excluding afatinib, a non–HER2-specific TKI, from the analysis, sensitivity analysis revealed a significant PFS benefit favoring TKI-containing regimens in patients with brain metastases.1

These findings imply that anti-HER2 TKI treatments provide equivalent overall survival and PFS benefits in patients with and without brain metastases.1 In patients with brain metastases, a sensitivity analysis that included only trials evaluating regimens containing tucatinib, lapatinib, or pyrotinib revealed a significant PFS benefit favoring TKI-containing regimens, emphasizing the importance of central nervous system involvement in interpreting the results of studies evaluating this class of agents.1

Reference

  1. Shagisultanova E, Gradishar W, Brown-Glaberman U, et al. Efficacy of tyrosine kinase inhibitors (TKI) in the treatment of patients with HER2-positive (HER2+) breast cancer with or without brain metastases: a systematic review and meta-analysis. 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021. P1-21-03.

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