Safety profile of Pertuzumab with Trastuzumab and Docetaxel in patients from Asia with human epidermal growth factor receptor 2-positive metastatic breast cancer: results from the phase III trial CLEOPATRA.

Author(s): Swain SM(1), Im YH(2), Im SA(2), Chan V(2), Miles D(2), Knott A(2), Clark E(2), Ross G(2), Baselga J(2).

Affiliation(s): Author information: (1)Washington Cancer Institute, MedStar Washington Hospital Center, Washington, D.C., USA; Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Division of Hematology and Medical Oncology, Department of Internal Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Veterans Memorial Medical Center, Cancer Research Center, Quezon City, Philippines; Mount Vernon Cancer Centre, Middlesex, United Kingdom; Roche Products Ltd., Welwyn Garden City, United Kingdom; Memorial Sloan-Kettering Cancer Center, Memorial Hospital, New York, New York, USA Sandra.M.Swain@MedStar.net. (2)Washington Cancer Institute, MedStar Washington Hospital Center, Washington, D.C., USA; Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Division of Hematology and Medical Oncology, Department of Internal Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Veterans Memorial Medical Center, Cancer Research Center, Quezon City, Philippines; Mount Vernon Cancer Centre, Middlesex, United Kingdom; Roche Products Ltd., Welwyn Garden City, United Kingdom; Memorial Sloan-Kettering Cancer Center, Memorial Hospital, New York, New York, USA.

Publication date & source: 2014, Oncologist. , 19(7):693-701

INTRODUCTION: We report detailed safety analyses by geographic region from the phase III study CLEOPATRA with pertuzumab, trastuzumab, and docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive first-line metastatic breast cancer. PATIENTS AND METHODS: Patients received pertuzumab/placebo at 840 mg in cycle 1 and 420 mg in subsequent cycles, and trastuzumab at 8 mg/kg in cycle 1 and 6 mg/kg in subsequent cycles; docetaxel was initiated at 75 mg/m(2). All study drugs were given intravenously, 3 times weekly. RESULTS: Docetaxel dose reductions below 75 mg/m(2) were more common in patients from Asia (47.0%) than other regions (13.4%); docetaxel dose escalations to 100 mg/m(2) were less frequent in Asia (2.4%) than other regions (18.7%). Rates of edema (26.1% and 5.4% for Asia and other regions, respectively), myalgia (42.3%, 14.7%), nail disorder (39.9%, 15.1%), febrile neutropenia (18.6%, 7.1%), upper respiratory tract infection (25.7%, 10.2%), decreased appetite (47.0%, 19.1%), and rash (44.3%, 22.0%) were at least twice as high in Asia as in other regions. Adverse events did not result in a reduction in the median number of study treatment cycles administered in patients from Asia. Efficacy analyses per region showed hazard ratios similar to those of the whole intention-to-treat (ITT) population for progression-free survival (ITT: 0.63; Asia: 0.68; other regions: 0.61) and overall survival (ITT: 0.66; Asia: 0.64; other regions: 0.66). CONCLUSION: Despite a higher proportion of docetaxel dose reductions in patients from Asia, survival benefits were comparable between regions. The benefit-risk profile of pertuzumab, trastuzumab, and docetaxel supports this regimen as the first-line therapy for patients with HER2-positive metastatic breast cancer from all geographic regions.