Phase III trial of nonpegylated liposomal doxorubicin in combination with trastuzumab and paclitaxel in HER2-positive metastatic breast cancer Journal Article
| Authors: | Baselga, J.; Manikhas, A.; Cortés, J.; Llombart, A.; Roman, L.; Semiglazov, V. F.; Byakhov, M.; Lokanatha, D.; Forenza, S.; Goldfarb, R. H.; Matera, J.; Azarnia, N.; Hudis, C. A.; Rozencweig, M. |
| Article Title: | Phase III trial of nonpegylated liposomal doxorubicin in combination with trastuzumab and paclitaxel in HER2-positive metastatic breast cancer |
| Abstract: | Background: 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 and Methods: Patients were randomly assigned to NPLD (M, 50 mg/m2 every 3 weeks for six cycles), trastuzumab (T, 4 mg/kg loading dose followed by 2 mg/kg weekly), and paclitaxel (P, 80 mg/m2 weekly) or T + P at the same doses until progression or toxicity. The primary efficacy outcome was progression-free survival (PFS). Results: 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. Conclusion(s): 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. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. |
| Keywords: | controlled study; treatment failure; major clinical study; overall survival; constipation; disease course; fatigue; paresthesia; doxorubicin; diarrhea; drug efficacy; heart left ventricle failure; hypertension; paclitaxel; cancer incidence; prospective study; progression free survival; computer assisted tomography; multiple cycle treatment; sensory neuropathy; breast cancer; bone marrow suppression; nausea; randomized controlled trial; stomatitis; vomiting; peripheral neuropathy; epidermal growth factor receptor 2; hemoglobin; arthralgia; asthenia; coughing; dyspnea; febrile neutropenia; fever; nail disease; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; neutrophil; cardiotoxicity; peripheral edema; erythema; flu like syndrome; headache; phase 3 clinical trial; estrogen receptor; progesterone receptor; trastuzumab; hormone receptor; dyspepsia; dry skin; anthracyclines; alopecia; epistaxis; bilirubin blood level; leukocyte; respiratory tract infection; leg pain; her2; rhinopharyngitis; onycholysis; decreased appetite; rhinorrhea; cardiac safety; human; priority journal; article; myocet; her2 positive metastatic breast cancer |
| Journal Title: | Annals of Oncology |
| Volume: | 25 |
| Issue: | 3 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2014-03-01 |
| Start Page: | 592 |
| End Page: | 598 |
| Language: | English |
| DOI: | 10.1093/annonc/mdt543 |
| PROVIDER: | scopus |
| PUBMED: | 24401928 |
| PMCID: | PMC4433508 |
| DOI/URL: | |
| Notes: | Export Date: 2 April 2014 -- Art. No.: mdt543 -- CODEN: ANONE -- Source: Scopus |
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