Updated Outcomes of Tucatinib versus Placebo Added to Trastuzumab and Capecitabine (HER2CLIMB) in Patients with Previously Treated HER2-Positive Metastatic Breast Cancer with Brain Metastases

Tucatinib is an oral tyrosine kinase inhibitor that has been licensed for use in conjunction with trastuzumab and capecitabine in patients with advanced or metastatic HER2-positive breast cancer, including patients with brain metastases, who have had ≥1 previous anti-HER2–based regimens in the metastatic context.1 Tucatinib significantly improved progression-free survival (PFS) and overall survival (OS) in patients with HER2-positive metastatic breast cancer in the HER2CLIMB study, including patients with untreated, treated stable, and treated advancing brain metastases.1 With an additional 15.6 months of follow-up, the inclusion of tucatinib among the whole study cohort continued to exhibit a clinically relevant extension of PFS and OS.1 The results of exploratory efficacy assessments in patients with brain metastases have been revised.1

A baseline brain MRI was performed on all patients in the HER2CLIMB study.1 Patients with brain metastases were eligible for inclusion, and they were divided into 3 groups: those who were untreated, those who were treated and stable, and those who were treated and their disease was still progressing.1 Tucatinib 300 mg twice daily or placebo in conjunction with trastuzumab and capecitabine was given to patients in a 2:1 ratio.1

Following the primary analysis, the protocol was changed to allow crossover from the placebo to the tucatinib regimen and to unblind sites to treatment assignment.1 Efficacy analyses were performed in patients with brain metastases at baseline, approximately 2 years after the last patient was randomized, using RECIST version 1.1 on the brain based on investigator evaluation.1 All patients with brain metastases had their OS and central nervous system (CNS)-PFS (brain progression or death) assessed.1 At the latest brain MRI, patients without CNS-PFS events were censored.1 In patients with demonstrable intracranial (IC) illness, the confirmed objective response rate-IC was assessed.1

At a median of 29.6 months, median OS was 21.6 months compared with 12.5 months in all patients with brain metastases, 21.4 months compared with 11.8 months in patients with untreated/treated advancing brain metastases, and 21.6 months compared with 16.4 months in patients with treated stable brain metastases.1 All patients with brain metastases had a median CNS-PFS of 9.9 months compared with 4.2 months, 9.6 months compared with 4.0 months in patients with untreated/treated advancing brain metastases, and 13.9 months compared with 5.6 months in patients with treated stable brain metastases.1 For patients with brain metastases, objective response rate-IC was greater in the tucatinib arm (47.3%) than in the placebo arm (20.0%), and median duration of response was 8.6 months compared with 3.0 months.1

The tucatinib-trastuzumab-capecitabine regimen resulted in a substantial and permanent extension of OS for all patients with HER2-positive metastatic breast cancer with brain metastases after a subsequent 15.6 months of follow-up.1 This effect was maintained in patients with untreated/treated advancing brain metastases as well as individuals with treated stable brain metastases.1 Tucatinib treatment continued, as it did in the primary analysis, to show clinically significant benefit in CNS-PFS.1

Reference

  1. Lin NU, Murthy RK, Abramson V, et al. Updated results of tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated HER2-positive metastatic breast cancer with brain metastases (HER2CLIMB). 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021. PD4-04.

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