| General information |
| Database: | DB01074 |
| Objective: | Vinflunine As Monotherapy or in Combination with Trastuzumab as FirstLine Treatment of Metastatic Breast Cancer |
| Authors: | Denise A. Yardley |
| Title: | a phase II trial of vinflunine as monotherapy or in combination with trastuzumab as firstline treatment of metastatic breast cancer. |
| Journal: | Cancer Investigation |
| Year: | 2010 |
| PMID: | 20690806 |
| Trial Design |
| Clinical Trial Id: | NCT00284180 |
| Agent: | trastuzumab
|
| Target: | Receptor proteintyrosine kinase erbB2
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | vinflunine as monotherapy or + trastuzumab |
| Study Type: | In thisphase II trial, they evaluated the efficacy of vinflunine as firstline treatment in patients with MBC. In addition, they evaluated the firstline efficacy of the vinflunine/trastuzumab combination in human epidermal growth factor receptor IIpositive patients. |
| Key Patients Feature: | female patients had to demonstrate a histologically or cytologically confirmed diagnosis ofMBC. Patients could not have received previous chemotherapy for metastatic disease. Previous neoadjuvant and/or adjuvant chemotherapy was permitted if all treatments had been completed more than and equal to 6 months prior to the documentation of recurrence. Previous hormonal therapy in the adjuvant setting and/or metastatic diseasewas permitted. If patients had received prior vinca alkaloid chemotherapy, all treatment had to have been administered more than 5 years prior to study initiation. Additional eligibility criteria included ECOG performance status of 0, 1, or 2; age more than and equal to 18 years; measurable disease (RECIST); adequate blood counts (absolute neutrophil count more than and equal to 1, 500/¦ÌL, platelets more than and equal to 100, 000/¦ÌL, and hemoglobin more than and equal to 10 g/dL); serum creatinine less than and equal to 1.5 mg/dL ¡Á institution upper limits of normal (ULN); adequate liver function (normal bilirubin; transaminases, and alkaline phosphatase < 2 ¡Á ULN); and serum creatinine less than and equal to 1.2 ¡Á ULN. |
| Biomarker: | human epidermal growth factor receptor 2positive |
| Biomark Analysis: | In human epidermal growth factor receptor 2positive patients, vinflunine/trastuzumab produced an objective response rate (33%), clinical benefit rate (71%), and progression free survival (6.2 months). |
| Control Group Info: | vinflunine as monotherapy or in combination with trastuzumab |
| Treatment Info: | Patients who were human epidermal growth factor receptor 2negative received vinflunine 320 mg/m2 intravenously (IV) on day 1 over 20 min, repeated every 21 days. human epidermal growth factor receptor 2 positive patients received treatment with vinflunine 280 mg/m2 every 21 days with trastuzumab administered with a loadingdoseof8mg/kg, followed by 6mg/kgIV on day 1 of each subsequent cycle, repeated every 21 days. If no grade 3/4 adverse events were encountered after the first cycle of vinflunine/trastuzumab, the dose of vinflunine could be escalated to 320 mg/m2. |
| Primary End Point: | the objective response rate. |
| Secondary End Point: | NA |
| Patients Number: | 32 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | the overall response rate in the human epidermal growth factor receptor 2positive patients was 33% with an additional 43% of patients demonstrating stable disease. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The group of human epidermal growth factor receptor 2negative patients treated with vinflunine monotherapy had median progression free of 3.2 months; In the human epidermal growth factor receptor 2positive group, median progression free survival was 6.2 months |
| Median OS A vs. C: | Median overall survival has not been reached for either vinflunine treatment arm. |
| Adverse Event(agent arm): | 44% of the patients experienced grade 3 or 4 neutropenia; however, prophylactic GCSF was not administered and there were no episodes of neutropenic fever and no grade 3/4 anemia or thrombocytopenia. The most common grade 3 nonhematologic toxicity consisted of pain in 11 patients (35%) attributed to treatment in six patients with five (13%) patients experiencing abdominal pain and one patient experiencing pain at the site of infusion. Grade 3 gastrointestinal toxicity included nausea and vomiting (9%), constipation (6%), diarrhea (6%), and ileus (3%). |
| Conclusions: | The vinfluninetrastuzumab combination was active and well tolerated, but our results do not suggest advantages over taxanetrastuzumab or vinorelbinetrastuzumab. |