Adjuvant pertuzumab and trastuzumab in early her2-positive breast cancer

APHINITY Steering Committee and Investigators, Alberto Ballestrero

Research output: Contribution to journalArticle

265 Citations (Scopus)

Abstract

BACKGROUND Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. METHODS We randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease-free survival rate of 91.8% with pertuzumab and 89.2% with placebo. RESULTS In the trial population, 63% of the patients who were randomly assigned to receive pertuzumab (2400 patients) or placebo (2405 patients) had node-positive disease and 36% had hormone-receptor-negative disease. Disease recurrence occurred in 171 patients (7.1%) in the pertuzumab group and 210 patients (8.7%) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.66 to 1.00; P = 0.045). The estimates of the 3-year rates of invasive-disease-free survival were 94.1% in the pertuzumab group and 93.2% in the placebo group. In the cohort of patients with node-positive disease, the 3-year rate of invasive-disease-free survival was 92.0% in the pertuzumab group, as compared with 90.2% in the placebo group (hazard ratio for an invasive-disease event, 0.77; 95% CI, 0.62 to 0.96; P = 0.02). In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease-free survival was 97.5% in the pertuzumab group and 98.4% in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95% CI, 0.68 to 1.86; P = 0.64). Heart failure, cardiac death, and cardiac dysfunction were infrequent in both treatment groups. Diarrhea of grade 3 or higher occurred almost exclusively during chemotherapy and was more frequent with pertuzumab than with placebo (9.8% vs. 3.7%). CONCLUSIONS Pertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to trastuzumab and chemotherapy. Diarrhea was more common with pertuzumab than with placebo. (Funded by F. Hoffmann-La Roche/Genentech; APHINITY ClinicalTrials.gov number, NCT01358877.)

Original languageEnglish
Pages (from-to)122-131
Number of pages10
JournalNew England Journal of Medicine
Volume377
Issue number2
DOIs
Publication statusPublished - Jul 13 2017

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Breast Neoplasms
Placebos
Disease-Free Survival
Confidence Intervals
Adjuvant Chemotherapy
Drug Therapy
pertuzumab
Trastuzumab
Diarrhea
Therapeutics
Survival Rate
Heart Failure
Hormones
Recurrence
Survival
human ERBB2 protein
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Adjuvant pertuzumab and trastuzumab in early her2-positive breast cancer. / APHINITY Steering Committee and Investigators ; Ballestrero, Alberto.

In: New England Journal of Medicine, Vol. 377, No. 2, 13.07.2017, p. 122-131.

Research output: Contribution to journalArticle

APHINITY Steering Committee and Investigators ; Ballestrero, Alberto. / Adjuvant pertuzumab and trastuzumab in early her2-positive breast cancer. In: New England Journal of Medicine. 2017 ; Vol. 377, No. 2. pp. 122-131.
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abstract = "BACKGROUND Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. METHODS We randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease-free survival rate of 91.8{\%} with pertuzumab and 89.2{\%} with placebo. RESULTS In the trial population, 63{\%} of the patients who were randomly assigned to receive pertuzumab (2400 patients) or placebo (2405 patients) had node-positive disease and 36{\%} had hormone-receptor-negative disease. Disease recurrence occurred in 171 patients (7.1{\%}) in the pertuzumab group and 210 patients (8.7{\%}) in the placebo group (hazard ratio, 0.81; 95{\%} confidence interval [CI], 0.66 to 1.00; P = 0.045). The estimates of the 3-year rates of invasive-disease-free survival were 94.1{\%} in the pertuzumab group and 93.2{\%} in the placebo group. In the cohort of patients with node-positive disease, the 3-year rate of invasive-disease-free survival was 92.0{\%} in the pertuzumab group, as compared with 90.2{\%} in the placebo group (hazard ratio for an invasive-disease event, 0.77; 95{\%} CI, 0.62 to 0.96; P = 0.02). In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease-free survival was 97.5{\%} in the pertuzumab group and 98.4{\%} in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95{\%} CI, 0.68 to 1.86; P = 0.64). Heart failure, cardiac death, and cardiac dysfunction were infrequent in both treatment groups. Diarrhea of grade 3 or higher occurred almost exclusively during chemotherapy and was more frequent with pertuzumab than with placebo (9.8{\%} vs. 3.7{\%}). CONCLUSIONS Pertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to trastuzumab and chemotherapy. Diarrhea was more common with pertuzumab than with placebo. (Funded by F. Hoffmann-La Roche/Genentech; APHINITY ClinicalTrials.gov number, NCT01358877.)",
author = "{Von Minckwitz}, Gunter and Marion Procter and {De Azambuja}, Evandro and Dimitrios Zardavas and Mark Benyunes and Giuseppe Viale and Thomas Suter and Amal Arahmani and Nathalie Rouchet and Emma Clark and Adam Knott and Istvan Lang and Christelle Levy and Yardley, {Denise A.} and Jose Bines and Gelber, {Richard D.} and Martine Piccart and Jose Baselga and {APHINITY Steering Committee and Investigators} and Alberto Ballestrero",
year = "2017",
month = "7",
day = "13",
doi = "10.1056/NEJMoa1703643",
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T1 - Adjuvant pertuzumab and trastuzumab in early her2-positive breast cancer

AU - Von Minckwitz, Gunter

AU - Procter, Marion

AU - De Azambuja, Evandro

AU - Zardavas, Dimitrios

AU - Benyunes, Mark

AU - Viale, Giuseppe

AU - Suter, Thomas

AU - Arahmani, Amal

AU - Rouchet, Nathalie

AU - Clark, Emma

AU - Knott, Adam

AU - Lang, Istvan

AU - Levy, Christelle

AU - Yardley, Denise A.

AU - Bines, Jose

AU - Gelber, Richard D.

AU - Piccart, Martine

AU - Baselga, Jose

AU - APHINITY Steering Committee and Investigators

AU - Ballestrero, Alberto

PY - 2017/7/13

Y1 - 2017/7/13

N2 - BACKGROUND Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. METHODS We randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease-free survival rate of 91.8% with pertuzumab and 89.2% with placebo. RESULTS In the trial population, 63% of the patients who were randomly assigned to receive pertuzumab (2400 patients) or placebo (2405 patients) had node-positive disease and 36% had hormone-receptor-negative disease. Disease recurrence occurred in 171 patients (7.1%) in the pertuzumab group and 210 patients (8.7%) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.66 to 1.00; P = 0.045). The estimates of the 3-year rates of invasive-disease-free survival were 94.1% in the pertuzumab group and 93.2% in the placebo group. In the cohort of patients with node-positive disease, the 3-year rate of invasive-disease-free survival was 92.0% in the pertuzumab group, as compared with 90.2% in the placebo group (hazard ratio for an invasive-disease event, 0.77; 95% CI, 0.62 to 0.96; P = 0.02). In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease-free survival was 97.5% in the pertuzumab group and 98.4% in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95% CI, 0.68 to 1.86; P = 0.64). Heart failure, cardiac death, and cardiac dysfunction were infrequent in both treatment groups. Diarrhea of grade 3 or higher occurred almost exclusively during chemotherapy and was more frequent with pertuzumab than with placebo (9.8% vs. 3.7%). CONCLUSIONS Pertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to trastuzumab and chemotherapy. Diarrhea was more common with pertuzumab than with placebo. (Funded by F. Hoffmann-La Roche/Genentech; APHINITY ClinicalTrials.gov number, NCT01358877.)

AB - BACKGROUND Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. METHODS We randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease-free survival rate of 91.8% with pertuzumab and 89.2% with placebo. RESULTS In the trial population, 63% of the patients who were randomly assigned to receive pertuzumab (2400 patients) or placebo (2405 patients) had node-positive disease and 36% had hormone-receptor-negative disease. Disease recurrence occurred in 171 patients (7.1%) in the pertuzumab group and 210 patients (8.7%) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.66 to 1.00; P = 0.045). The estimates of the 3-year rates of invasive-disease-free survival were 94.1% in the pertuzumab group and 93.2% in the placebo group. In the cohort of patients with node-positive disease, the 3-year rate of invasive-disease-free survival was 92.0% in the pertuzumab group, as compared with 90.2% in the placebo group (hazard ratio for an invasive-disease event, 0.77; 95% CI, 0.62 to 0.96; P = 0.02). In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease-free survival was 97.5% in the pertuzumab group and 98.4% in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95% CI, 0.68 to 1.86; P = 0.64). Heart failure, cardiac death, and cardiac dysfunction were infrequent in both treatment groups. Diarrhea of grade 3 or higher occurred almost exclusively during chemotherapy and was more frequent with pertuzumab than with placebo (9.8% vs. 3.7%). CONCLUSIONS Pertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to trastuzumab and chemotherapy. Diarrhea was more common with pertuzumab than with placebo. (Funded by F. Hoffmann-La Roche/Genentech; APHINITY ClinicalTrials.gov number, NCT01358877.)

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