Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial
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Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. / Lin, Nancy U; Borges, Virginia; Anders, Carey; Murthy, Rashmi K; Paplomata, Elisavet; Hamilton, Erika; Hurvitz, Sara; Loi, Sherene; Okines, Alicia; Abramson, Vandana; Bedard, Philippe L; Oliveira, Mafalda; Mueller, Volkmar; Zelnak, Amelia; DiGiovanna, Michael P; Bachelot, Thomas; Chien, A Jo; O'Regan, Ruth; Wardley, Andrew; Conlin, Alison; Cameron, David; Carey, Lisa; Curigliano, Giuseppe; Gelmon, Karen; Loibl, Sibylle; Mayor, JoAl; McGoldrick, Suzanne; An, Xuebei; Winer, Eric P.
in: J CLIN ONCOL, Jahrgang 38, Nr. 23, 10.08.2020, S. 2610-2619.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial
AU - Lin, Nancy U
AU - Borges, Virginia
AU - Anders, Carey
AU - Murthy, Rashmi K
AU - Paplomata, Elisavet
AU - Hamilton, Erika
AU - Hurvitz, Sara
AU - Loi, Sherene
AU - Okines, Alicia
AU - Abramson, Vandana
AU - Bedard, Philippe L
AU - Oliveira, Mafalda
AU - Mueller, Volkmar
AU - Zelnak, Amelia
AU - DiGiovanna, Michael P
AU - Bachelot, Thomas
AU - Chien, A Jo
AU - O'Regan, Ruth
AU - Wardley, Andrew
AU - Conlin, Alison
AU - Cameron, David
AU - Carey, Lisa
AU - Curigliano, Giuseppe
AU - Gelmon, Karen
AU - Loibl, Sibylle
AU - Mayor, JoAl
AU - McGoldrick, Suzanne
AU - An, Xuebei
AU - Winer, Eric P
PY - 2020/8/10
Y1 - 2020/8/10
N2 - 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 < .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).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.
AB - 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 < .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).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.
U2 - 10.1200/JCO.20.00775
DO - 10.1200/JCO.20.00775
M3 - SCORING: Journal article
C2 - 32468955
VL - 38
SP - 2610
EP - 2619
JO - J CLIN ONCOL
JF - J CLIN ONCOL
SN - 0732-183X
IS - 23
ER -
