Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial

Abstract

<jats:sec><jats:title>PURPOSE</jats:title><jats:p> In the HER2CLIMB study, patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer with brain metastases (BMs) showed statistically significant improvement in progression-free survival (PFS) with tucatinib. We describe exploratory analyses of intracranial efficacy and survival in participants with BMs. </jats:p></jats:sec><jats:sec><jats:title>PATIENTS AND METHODS</jats:title><jats:p> Patients were randomly assigned 2:1 to tucatinib or placebo, in combination with trastuzumab and capecitabine. All patients underwent baseline brain magnetic resonance imaging; those with BMs were classified as active or stable. Efficacy analyses were performed by applying RECIST 1.1 criteria to CNS target lesions by investigator assessment. CNS-PFS (intracranial progression or death) and overall survival (OS) were evaluated in all patients with BMs. Confirmed intracranial objective response rate (ORR-IC) was evaluated in patients with measurable intracranial disease. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> There were 291 patients with BMs: 198 (48%) in the tucatinib arm and 93 (46%) in the control arm. The risk of intracranial progression or death was reduced by 68% in the tucatinib arm (hazard ratio [HR], 0.32; 95% CI, 0.22 to 0.48; P &lt; .0001). Median CNS-PFS was 9.9 months in the tucatinib arm versus 4.2 months in the control arm. Risk of death was reduced by 42% in the tucatinib arm (OS HR, 0.58; 95% CI, 0.40 to 0.85; P = .005). Median OS was 18.1 versus 12.0 months. ORR-IC was higher in the tucatinib arm (47.3%; 95% CI, 33.7% to 61.2%) versus the control arm (20.0%; 95% CI, 5.7% to 43.7%; P = .03). </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> In patients with HER2-positive breast cancer with BMs, the addition of tucatinib to trastuzumab and capecitabine doubled ORR-IC, reduced risk of intracranial progression or death by two thirds, and reduced risk of death by nearly half. To our knowledge, this is the first regimen to demonstrate improved antitumor activity against BMs in patients with HER2-positive breast cancer in a randomized, controlled trial. </jats:p></jats:sec>

Characteristics and Clinical Outcome of Breast Cancer Patients with Asymptomatic Brain Metastases

“…The HER2CLIMB Trial [ 23 ] examining the tyrosine kinase inhibitor tucatinib in addition to standard therapy allowed the inclusion of patients with stable BM. The encouraging results concerning the decreased intracranial progression rate, increased OS, as well as reduced risk of death under treatment with the novel compound tucatinib indicates a potential rationale for BM early detection strategies since patients might benefit more from specific therapies.…”

Update Breast Cancer 2020 Part 4 – Advanced Breast Cancer

“…In patients who were treated with tucatinib + trastuzumab + capecitabine, the median CNS-related progression-free survival was prolonged from 4.2 to 9.9 months. The hazard ratio was 0.32 (95% CI: 0.22 – 0.48) 7 . The median overall survival was prolonged from 12.0 to 18.1 months.…”

“…Bei Patientinnen, welche mit Tucatinib + Trastuzumab + Capecitabin behandelt wurden, konnte das mediane ZNS-bezogene progressionsfreie Überleben von 4,2 auf 9,9 Monate verlängert werden. Die Hazard Ratio betrug 0,32 (95%-KI: 0,22 – 0,48) 7 . Auch das mediane Gesamtüberleben konnte von 12,0 auf 18,1 Monate verlängert werden.…”

Use of HER2-Directed Therapy in Metastatic Breast Cancer and How Community Physicians Collaborate to Improve Care

“…In the HER2CLIMB study, 291 patients were enrolled who had brain metastases—48% in the tucatinib arm and 46% in the control arm. The CNS (central nervous system) progression-free survival and median overall survival favored the tucatinib arm making this an important therapy in patients with HER2+ breast cancer metastatic to brain [ 31 ].…”