Entry Detail
| General information | |
| Database: | DB01068 |
| Objective: | Sunitinib in combination with trastuzumab for the treatment of advanced breast cancer |
| Authors: | Thomas Bachelot |
| Title: | Sunitinib in combination with trastuzumab for the treatment of advanced breast cancer: activity and safety results from a phase II study. |
| Journal: | BMC cancer |
| Year: | 2014 |
| PMID: | 24606768 |
| Trial Design | |
| Clinical Trial Id: | NCT00243503 |
| Agent: | sunitinib |
| Target: | FL cytokine receptor Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 Plateletderived growth factor receptor |
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | Sunitinib + trastuzumab |
| Study Type: | Originally developed using a randomized, placebocontrolled design (control arm: trastuzumab plus placebo; test arm: trastuzumab plus sunitinib), the study was subsequently changed to an openlabel, singlearm design in response to evolving standards of care in which singleagent trastuzumab was considered suboptimal for patient treatment. |
| Key Patients Feature: | Eligible patients were female aged more than and equal to 18 years with histologically or cytologically proven, unresectable, locally recurrent or metastatic human epidermal growth factor receptor 2positive BC and measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) [30]. The study also included patients who may have had prior trastuzumab and/or lapatinib treatment in the neoadjuvant, adjuvant, or metastatic disease setting, or prior treatment with hormone therapy in the adjuvant and/or advanced disease setting. patients were required to have an Eastern Cooperative Oncology Group performance status of 0 or 1 with adequate organ function (including left ventricular ejection fraction [LVEF] more than and equal to 55%) and resolution of all acute toxic effects of prior therapy or surgical procedures to National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (NCI CTCAE v3.0) grade less than and equal to 1 (except alopecia). |
| Biomarker: | human epidermal growth factor receptor 2positive |
| Biomark Analysis: | Sunitinib plus trastuzumab demonstrated antitumor activity in patients with human epidermal growth factor receptor 2positive ABC, particularly those who were treatmentna ve or had only received prior adjuvant treatment |
| Control Group Info: | single arm |
| Treatment Info: | sunitinib 37.5 mg/day and trastuzumab administered either weekly (loading, 4 mg/kg; then weekly 2 mg/kg) or 3weekly (loading, 8 mg/kg; then 3weekly 6 mg/kg). Prior trastuzumab and/or lapatinib treatment were permitted. |
| Primary End Point: | ORR based on RECIST. |
| Secondary End Point: | duration of tumor response, CBR, progression free survival (PFS), overall survival (OS), safety, pharmacokinetics (PK), and patientreported outcomes (PROs). |
| Patients Number: | 60 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 37%; 95% CI 24-51 |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | median PFS was 6.4 months |
| Median OS A vs. C: | Median OS had not yet been reached |
| Adverse Event(agent arm): | The most commonly reported nonhematologic AEs of any cause were fatigue/asthenia (75%), diarrhea (60%), and stomatitis/related oral disorders (53%). The most common nonhematologic grade 3 AEs were fatigue/ asthenia (20%), hypertension (13%), and decreased appetite (7%). There were six nonhematologic grade 4 AEs (LVEF decline, pulmonary embolism, hyponatremia, multiorgan failure, aspartate aminotransferase increase, and pancreatitis). One patient died on study from cardiogenic shock; prior to enrolling in the present study, this patient had received a combination of fluorouracil, cyclophosphamide, and epirubicin in the adjuvant setting and trastuzumab followed by lapatinib in the advanced/metastatic setting. |
| Conclusions: | Sunitinib plus trastuzumab demonstrated antitumor activity in patients with human epidermal growth factor receptor 2positive ABC, particularly those who they were treatmentna?ve or had only received prior adjuvant treatment. Sunitinib plus trastuzumab had acceptable safety and tolerability in patients with human epidermal growth factor receptor 2positive ABC who had not received prior anthracycline therapy. |