Entry Detail
| General information | |
| Database: | DB01041 |
| Objective: | Impact of adding the sorafenib to endocrine therapy in metastatic estrogen receptorpositive breast cancer |
| Authors: | Suleiman Massartheyh |
| Title: | Impact of adding the multikinase inhibitor sorafenib to endocrine therapy in metastatic estrogen receptorpositive breast cancer. |
| Journal: | future oncology |
| Year: | 2014 |
| PMID: | 24826798 |
| Trial Design | |
| Clinical Trial Id: | NCT00525161 |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 17 |
| Therapeutic Combination Content: | sorafenib plus endocrine therapy |
| Study Type: | originally a singleinstitution, pilot, phase II study of adding sorafenib to pre existing endocrine therapy. |
| Key Patients Feature: | Premenopausal or postmenopausal patients were required to have biopsyproven metastatic ERpositive breast cancer and already receiving an endocrine agent. patients were required to have either progressive disease (PD) or maximal response on the existing endocrine agent with measurable residual disease. patients were required to have an Eastern Cooperative Oncology Group performance status of 0-2 and adequate baseline renal and hepatic function, defined as serum creatinine less than and equal to 1.5times the upper limit of normal (ULN), serum bilirubin less than and equal to 1.5times the ULN and aspartate aminotransferase-alanine aminotransferase ratio less than and equal to 2.5times the ULN. |
| Biomarker: | estrogen receptorpositive |
| Biomark Analysis: | The serum samples demonstrated a significant reduction in VEGF receptor 2 and PDGF receptor¦Á. Microarray analysis identified 32 suppressed genes, no induced genes and 29 enriched Kyoto Encyclopedia of Genes and Genomes pathways. |
| Control Group Info: | single arm |
| Treatment Info: | Sorafenib dose was 400 mg orally twice daily along with continuing the same endocrine agent. |
| Primary End Point: | RECIST after 3 months of sorafenib. |
| Secondary End Point: | safety, time to progression and biomarker modulation. |
| Patients Number: | 11 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Hypophosphatemia was the most common AE, followed by hypokalemia. weight loss and rash, including one patient with a Stevens- Johnsonlike reaction, were the most common clinical AEs encountered, followed by hypertension. Overall, the majority of toxicities were grade 1 or 2, with seven grade 3 toxicities seen: two hypophosphatemia episodes and one each of rash, anorexia, weight loss, colitis and hypokalemia. There were no grade 4 toxicities and no patients experienced hand-foot syndrome. |
| Conclusions: | The strategy of adding a targeted agent to endocrine therapy upon resistance may be worthwhile testing in larger studies. |