| General information |
| Database: | DB01073 |
| Objective: | trastuzumab in combination with everolimus (RAD001) in patients with human epidermal growth factor receptor 2overexpressing metastatic breast cancer who progressed on trastuzumabbased therapy. |
| Authors: | Phuong K. Morrow |
| Title: | Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with human epidermal growth factor receptor 2overexpressing metastatic breast cancer who progressed on trastuzumabbased therapy. |
| Journal: | journal of clinical oncology |
| Year: | 2011 |
| PMID: | 21730275 |
| Trial Design |
| Clinical Trial Id: | NCT00317720 |
| Agent: | Trastuzumab Emtansine
|
| Target: | human epidermal growth factor receptor 2 and microtubuleinhibitory
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | trastuzumab + everolimus (RAD001) |
| Study Type: | openlabelphase I/II study was approved by the local institutional review board at each institution. |
| Key Patients Feature: | Eligible women were more than and equal to 18 years of age with history of biopsyproven human epidermal growth factor receptor 2overexpressing breast cancer (determined by immunohistochemistry [score, 3+] or by fluorescence in situ hybridization [her2/neu to chromosome 17 ratio>2]) and radiographic evidence ofmetastatic breast cancer (MBC). patients were required to have an Eastern Cooperative Oncology Group performance status of less than and equal to 2; more than and equal to 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors, and could not receive investigational agents within 15 days of enrollment. Eligible patients had adequate hematologic, renal, hepatic, and cardiac function. |
| Biomarker: | evaluated expression and/or phosphorylation status of PTEN, mTOR, Akt, and p70S6 kinase by immunohistochemistry. |
| Biomark Analysis: | Patients with PTEN loss demonstrated decreased overall survival (P = .048). however, PFS was not affected by PTEN loss |
| Control Group Info: | single arm |
| Treatment Info: | If a patient was on trastuzumab at time of registration, the loading dose oftrastuzumab was deferred, and she received the maintenance dose (6 mg/kg every 3 weeks). If the last trastuzumab dose was given 1 week (for patients receiving 2 mg/kg/wk), or 3 weeks before registration (for patients receiving 6mg/kgevery3weeks), the patient received a loading dose (8mg/kg) followed by the maintenance dose. Institutionspecific study designs are specified as follows. |
| Primary End Point: | identify the optimal dose of everolimus in combination with trastuzumab, and determine the efficacy ofeverolimus plus trastuzumab in patients with human epidermal growth factor receptor 2expressing tumors with resistance to trastuzumabbased therapy for MBC. Efficacy was measured by the clinical benefit response rate (CBR), defined as confirmed CR plus PR at anytime plus persistent SD(pSD). |
| Secondary End Point: | NA |
| Patients Number: | 47 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS was 4.1 months. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Fatigue, infection, and mucositis were the predominant nonhematologic toxicities. Grade 2 hematologic toxicity was common, accounting for 13% to 17% of patients. No significant cardiovascular toxicity was noted. There were no treatment related deaths. Dose reductions/delays occurred in 25 patients (53%). Themost common causes for alterations in dosing schedule were (in order of frequency): mucositis, rash, and infection. Among the patients who required dose delays, 10 (40%) required more than and equal to 2 dose delays while being treated on the trial; average length ofdose delay was 9 days. |
| Conclusions: | Inhibition of mTOR results in clinical benefit and disease response in patients with trastuzumabresistant human epidermal growth factor receptor 2overexpressing MBC. |