| General information |
| Database: | DB01027 |
| Objective: | Phase I-II study of vorinostat plus paclitaxel and bevacizumab in metastatic breast cancer. |
| Authors: | B. Ramaswamy |
| Title: | Phase III study of vorinostat plus paclitaxel and bevacizumab in metastatic breast cancer: evidence for vorinostatinduced tubulin acetylation and Hsp90 inhibition in vivo. |
| Journal: | Breast Cancer Res Treat |
| Year: | 2012 |
| PMID: | 22200869 |
| Trial Design |
| Clinical Trial Id: | NCT00368875 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 13 |
| Therapeutic Combination Content: | vorinostat plus paclitaxel and bevacizumab |
| Study Type: | a phase I-II clinical trial evaluating the combination of an intermittent schedule of vorinostat plus paclitaxel and bevacizumab as firstline therapy for MBC, which had previously been shown to be more effective than paclitaxel alone in this setting. |
| Key Patients Feature: | Patients with histologically or cytologically confirmed metastatic or surgically inoperable locally advanced human epidermal growth factor receptor 2negative breast cancer were eligible for the study. patients were required to have no prior chemotherapy for MBC and at least one measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0). Other eligibility criteria were similar to those used in the pivotal E2100 trial. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | vorinostat (200 or 300 mg PO BID) on days 1-3, 8-10, and 15-17, plus paclitaxel (90 mg/m2) on days 2, 9, 16, and bevacizumab (10 mg/kg) on days 2 and 16 every 28 days. |
| Primary End Point: | The primary endpoint of the phase I part of the study was to identify the recommendedphase II dose (RPTD) of vorinostat in combination with paclitaxel and bevacizumab. The primary endpoint of the phase II portion was objective response rate (ORR defined as complete response (CR) plus partial response (PR)). |
| Secondary End Point: | NA |
| Patients Number: | 50 |
| Trial Results |
| DLT_MTD: | No dose limiting toxicities were observed |
| Objective Response Rate: | 24 objective responses (55%, 95% confidence intervals [C.I.] 39 and 70%) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median progression free survival in all 54 treated patients was 11.9 months (95% CI = 8.9, 13.9 months) |
| Median OS A vs. C: | median overall survival was 29.4 months (95% CI. 25.6, 34.7 months) |
| Adverse Event(agent arm): | The most common grade 4 toxicities include neutropenia (7%), musculoskeletal pain (6%), thrombosis (4%), fatigue (2%), hypocalcemia (2%), proteinuria (2%), anemia (2%), and nasal septum perforation (2%). The most frequent grade 2-3 adverse events potentially attributed to vorinostat included fatigue (52%), nausea (31%), diarrhea (24%), anemia (24%), anorexia (20%), taste disturbances (19%), and rash (15%). Grade 2-3 hypertension was seen in 15% and headache in 13% of patients. |
| Conclusions: | In summary, our study provides evidence that vorinostat may be safely combined with paclitaxel and bevacizumab using an intermittent schedule and does not substantially enhance toxicity of paclitaxel-bevacizumab combination. |