Entry Detail
| General information | |
| Database: | DB01069 |
| Objective: | sunitinib in combination with capecitabine versus capecitabine monotherapy for the treatment of patients with pretreated metastatic breast cancer. |
| Authors: | John P. Crown |
| Title: | Phase III trial of sunitinib in combination with capecitabine versus capecitabine monotherapy for the treatment of patients with pretreated metastatic breast cancer. |
| Journal: | journal of clinical oncology |
| Year: | 2013 |
| PMID: | 23857972 |
| Trial Design | |
| Clinical Trial Id: | NCT00435409 |
| 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: | 2 |
| Therapeutic Combination Content: | sunitinib + capecitabine |
| Study Type: | multicenter, prospective openlabel study, patients were randomlyassigned I:I to receive sunitinib plus capecitabineorcapecitabine alone. |
| Key Patients Feature: | Eligible patients were age more than and equal to 18 years with a histologically or cytologically confirmed diagnosis of unresectable, locally advanced, or metastatic breast carcinoma; an Eastern Cooperative Oncology Group performance status of0 or 1; and evidence ofadequate organ function. Either measurable or evaluable boneonly disease was permitted. Patients must have had prior anthracycline and taxane treatment in the early or advanceddisease setting, with either relapse within 1 year ofneoadjuvant/adjuvant treatment or one to two prior chemotherapyregimens in the advanceddisease setting. Prior hormonal therapy was permitted if concurrent or sequential to adjuvant chemotherapy (hormone receptor-positive patients with boneonly disease must have experienced progression during or after hormone therapy). Human epidermal growth factor receptor 2-positive disease was permitted if previously treated with trastuzumab (continuation oftrastuzumab therapy beyond progression was not standard practice when the trial was designed). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | capecitabine monotherapy |
| Treatment Info: | In the combination arm, patients received capecitabine orally at a starting dose of 2, 000mg/m2 (1, 000 mg/m2 twice daily) on days 1 to 14 ofa 3week cycle plus sunitinib orally at a starting dose of 37.5 mg once daily. In the monotherapy arm, patients received capecitabine at a starting dose of 2, 500 mg/m2 (1, 250mg/m2 twice daily) on days 1 to 14 ofa 3week cycle. |
| Primary End Point: | PFS (defined as time from random assignment to first documented tumor progression or death during study as a result of any cause, whichever occurred first) based on independent blinded radiologic review. |
| Secondary End Point: | PFS (investigator assessment), ORR, duration of response, OS, and safety. |
| Patients Number: | 442 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | ORRs were similar between the treatment arms in patients with measurable disease basedonindependent radiologic review (19% v 18%; odds ratio, 1.04; 95% CI, 0.61 to 1.79; onesided exact P =0 .490) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | medians of 5.5 months (95% CI, 4.5 to 6.0) for the sunitinib plus capecitabine arm and 5.9 months (95% CI, 5.4 to 7.6) for the capecitabine monotherapy arm (hazard ratio, 1.22; 95% CI, 0.95 to 1.58; onesided P= .941). |
| Median OS A vs. C: | medians OS of 16.4 and 16.5 months (HR, 0.99;95%CI, 0.76 to 1.30; onesided logrank P=0.484) |
| Adverse Event(agent arm): | Hematologic AEs were more frequent and more severe with the sunitinib plus capecitabine combination than with capecitabine monotherapy. The frequencies of grade 3 or 4 neutropenia and thrombocytopenia were 31% and 17% in the combination arm and 4% and 0% in the monotherapy arm, respectively. Themost frequently reported grade 3 or 4 nonhematologic AEs in the combination arm were handfoot syndrome (16%), asthenia (12%), and fatigue (10%). Hypertension was also reported more frequently in the combination arm (22% v 4%), as was hypothyroidism (11% v 1%); both were mostly low grade in severity. In the capecitabine arm, the most frequently reported grade 3 or 4 nonhematologic AEs were handfoot syndrome (24%), diarrhea (10%), and vomiting (4%). |
| Conclusions: | The addition of sunitinib to capecitabine does not improve the clinical outcome of patients with MBC pretreated with anthracyclines and taxanes. |