Phase III trial of nonpegylated liposomal doxorubicin in combination with trastuzumab and paclitaxel in HER2-positive metastatic breast cancer
| Autor: | N. Azarnia, José Baselga, Alexey Manikhas, Vladimir Semiglazov, Clifford A. Hudis, R.H. Goldfarb, S. Forenza, M. Rozencweig, Javier Cortes, J. Matera, Mikhail Byakhov, L Roman, D. Lokanatha, Antonio Llombart |
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| Rok vydání: | 2019 |
| Předmět: |
Oncology
medicine.medical_specialty Paclitaxel Receptor ErbB-2 Liposomal Doxorubicin Breast Neoplasms Antibodies Monoclonal Humanized Disease-Free Survival Drug Administration Schedule Polyethylene Glycols chemistry.chemical_compound Breast cancer Trastuzumab Internal medicine Antineoplastic Combined Chemotherapy Protocols Medicine Humans Doxorubicin Progression-free survival Prospective Studies Neoplasm Metastasis skin and connective tissue diseases Cardiotoxicity Antibiotics Antineoplastic business.industry Hematology Original Articles medicine.disease Metastatic breast cancer Corrigenda Antineoplastic Agents Phytogenic Treatment Outcome chemistry cardiovascular system Female business medicine.drug |
| Zdroj: | Annals of Oncology |
| ISSN: | 1569-8041 |
| Popis: | Nonpegylated liposomal doxorubicin liposomal doxorubicin, (Myocet™; Sopherion Therapeutics, Inc Canada, and Cephalon, Europe) (NPLD; Myocet(®)) in combination with trastuzumabHerceptin(®) (Hoffmann-La Roche) has shown promising activity and cardiac safety. We conducted a randomized phase III trial of first-line NPLD plus trastuzumab and paclitaxel (Pharmachemie B.V.) (MTP) versus trastuzumab plus paclitaxel (TP) in patients with human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer.Patients were randomly assigned to NPLD (M, 50 mg/m(2) every 3 weeks for six cycles), trastuzumab (T, 4 mg/kg loading dose followed by 2 mg/kg weekly), and paclitaxel (P, 80 mg/m(2) weekly) or T + P at the same doses until progression or toxicity. The primary efficacy outcome was progression-free survival (PFS).One hundred and eighty-one patients were allocated to receive MTP, and 183 to TP. Median PFS was 16.1 and 14.5 months with MTP and TP, respectively [hazard ratio (HR) 0.84; two-sided P = 0.174]. In patients with estrogen receptor (ER)- and progesterone receptor (PR)-negative tumors, PFS was 20.7 and 14.0 months, respectively [HR 0.68; 95% confidence interval (CI) 0.47-0.99]. Median overall survival (OS) was 33.6 and 28.9 months with MTP and TP, respectively (HR 0.79; two-sided P = 0.083). In ER- and PR-negative tumors, OS was 38.2 and 27.9 months, respectively (HR 0.63; 95% CI 0.42-0.93). The frequency of adverse events was higher with MTP, but there was no significant difference in cardiac toxicity between treatment arms.The trial failed to demonstrate a significant clinical improvement with the addition of M to TP regimen. The clinical benefit observed in an exploratory analysis in the ER- and PR-negative population deserves consideration for further clinical trials.NCT00294996. |
| Databáze: | OpenAIRE |
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