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Pegylated Liposomal Doxorubicin Plus Docetaxel Significantly Improves Time To Progression Without Additive Cardiotoxicity Compared With Docetaxel Monotherapy In Patients With Advanced Breast Cancer Previously Treated With Neoadjuvant-Adjuvant Anthracycline Therapy: Results From A Randomized Phase III Study

Joseph A. Sparano, Anatoly N. Makhson, Vladimir F. Semiglazov, Sergei A. Tjulandin, Olga I. Balashova, Igor N. Bondarenko, Natalia V. Bogdanova, George M. Manikhas, Gennadiy P. Oliynychenko, Valery A. Chatikhine, Sen H. Zhuang, Liang Xiu, Zhilong Yuan, Wayne R. Rackoff

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PurposeTo determine whether the combination of pegylated liposomal doxorubicin (PLD) and docetaxel significantly prolongs time to disease progression compared with docetaxel alone without an increase in cardiac toxicity in women with advanced breast cancer who had experienced relapse at least 1 year after prior adjuvant or neoadjuvant anthracycline therapy.Patients and MethodsThis international, phase III study randomly assigned 751 patients to receive either docetaxel 75 mg/m2(n = 373) or PLD 30 mg/m2followed by docetaxel 60 mg/m2every 21 days (n = 378) and continued until disease progression or prohibitive toxicity. The primary end point was time to progression (TTP). Secondary end points were overall survival (OS), objective response rate (ORR), cardiac toxicity, and safety.ResultsTreatment with PLD-docetaxel significantly improved median TTP from 7.0 to 9.8 months (hazard ratio [HR] = 0.65; 95% CI, 0.55 to 0.77; P = .000001) and the ORR from 26% to 35% (P = .0085). OS was similar between the two groups (HR = 1.02; 95% CI, 0.86 to 1.22). The incidence of grade 3 or 4 adverse events were similar (78% v 72%), although a higher incidence of hand-foot syndrome (24% v 0%) and mucositis/stomatitis (12% v 1%) were observed in the PLD-docetaxel combination. Protocol-defined left ventricular ejection fraction decreases and congestive heart failure were reported in 5% and 1% in both treatment arms, respectively.ConclusionThe PLD-docetaxel combination was more effective than docetaxel alone in women with metastatic breast cancer who had experienced relapse at least 1 year after prior adjuvant anthracycline therapy without an increase in cardiac toxicity, although mucocutaneous toxicity was more common.