Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer
By G. von Minckwitz, M. Procter, E. de Azambuja, D. Zardavas, M. Benyunes, G. Viale, T. Suter, A. Arahmani, N. Rouchet, E. Clark and 8 more. New England Journal of Medicine, 2017
1,185 citations recorded by the source corpus.
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.)
Subfields: Cancer Research, Oncology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/59afcaf1f61b66ed25ec19b4010118db023bc71f
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cancer Research
In Oncology
In Pathology and Forensic Medicine
Citations in the corpus
- De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017 (2018, methodology): “Dual blockade with pertuzumab and trastuzumab improves outcome among patients who are at higher risk for relapse because of lymph-node involvement or hormone-receptor negativity [90].”
- Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline (2021, background): “5% improvement in invasive DFS with the addition of pertuzumab.(104)”
- Mechanisms of receptor tyrosine kinase activation in cancer (2018, positive): “cetuximab in lung cancer [181], panitumumab in colon cancer [182], cetuximab in head and neck cancer [183], trastuzumab and pertuzumab in breast cancer [184, 185].”
- Kinase-targeted cancer therapies: progress, challenges and future directions (2018, background): “body constructs targeting kinases include Trastuzumab and T-DM1 (targeting ERBB2/HER2) in breast and bladder cancer [175, 176], Bevacizumab (targeting VEGF) in ovarian, metastatic colon cancer and glioblastoma [177], Cetuximab, Panitumumab and necitumumab (targeting EGFR) in colorectal cancer and NS”