Intracranial Efficacy, Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Pos Breast Cancer With Brain Metastases

鈥� An ASCO Reading Room selection

March 2, 2021

Nancy U. Lin, MD; Virginia Borges, MMSc, MD; Carey Anders, MD; Rashmi K. Murthy, MD, MBE; Elisavet Paplomata, MD; Erika Hamilton, MD; Sara Hurvitz, MD; Sherene Loi, MD, PhD; Alicia Okines, MBChB, MD; Vandana Abramson, MD; Philippe L. Bedard, MD; Mafalda Oliveira, MD, PhD; Volkmar Mueller, MD; Amelia Zelnak, MD; Michael P. DiGiovanna, MD, PhD; Thomas Bachelot, MD; A. Jo Chien, MD; Ruth O鈥橰egan, MD; Andrew Wardley, MBChB, MSc, MD; Alison Conlin, MD, MPH; David Cameron, MD, MA; Lisa Carey, MD; Giuseppe Curigliano, MD, PhD; Karen Gelmon, MD; Sibylle Loibl, MD, PhD; JoAl Mayor, PharmD; Suzanne McGoldrick, MD, MPH; Xuebei An, PhD; and Eric P. Winer, MD

Journal of Clinical Oncology

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Purpose

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.

Patients and Methods

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.

Results

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 < 0.0001). 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 = 0.005). 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 = 0.03).

Conclusion

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.

Read an interview about the study here and expert commentary about the clinical implications here.

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Intracranial Efficacy, Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Pos Breast Cancer With Brain Metastases

Primary Source

Journal of Clinical Oncology

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