| General information |
| Database: | DB01078 |
| Objective: | combined fulvestrant and everolimus in patients with metastatic estrogen receptor (ER)positive breast cancer after aromatase inhibitor (AI) failure |
| Authors: | Suleiman Massartheyh |
| Title: | a phase II study of combined fulvestrant and everolimus in patients with metastatic estrogen receptor (ER)positive breast cancer after aromatase inhibitor (AI) failure. |
| Journal: | Breast Cancer Res Treat |
| Year: | 2014 |
| PMID: | 24327334 |
| Trial Design |
| Clinical Trial Id: | NCT00570921 |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | fulvestrant and everolimus |
| Study Type: | a singleinstitutionphase II study of combined fulvestrant and everolimus after AI failure, starting therapy concomitantly on day I of enrollment. |
| Key Patients Feature: | Postmenopausal patientswere required to havemetastaticERpositive breast cancer, measurable and/or evaluable disease, and disease progression or relapse on an AI within 6 months prior to enrollment. patients were required to have an ECOG performance status of 0-2 and adequate baseline renal and hepatic function, defined as serum creatinine less than and equal to 1.5 ¡Á upper limit of normal (ULN), serum bilirubin less than and equal to 1.5¡Á ULN, and ALT/AST less than and equal to 2.5¡Á ULN; adequate bone marrow function, defined as an absolute neutrophil count more than and equal to 1.5 ¡Á 109/l, platelet count>100, 000/ul, and hemoglobin>9 gm/dl; and an International Normalized Ratio of<1.3. |
| Biomarker: | estrogen receptor (ER)positive |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Fulvestrant was administered intramuscularly (in the gluteus maximus) in a loading dose schedule as follows: 500 mg in two divided doses¡ªone on each side on day 1, then 250 mg on day 14, and then 250 mg on day 28 and every 4 weeks ¡À 3 days thereafter. Everolimus was administered initially at a dose of 5 mg daily in the first 5patient cohort for the first month of treatment and then increased to 10 mg PO daily after that. |
| Primary End Point: | time to progression (TTP) |
| Secondary End Point: | objective response rate, clinical benefit rate (CBR), safety, and biomarker correlates. |
| Patients Number: | 31 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 0.13 |
| Disease Control Rate: | CBR of 49 % |
| Median Time to Progression: | 7.4 months (95 % CI 1.912.1) |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Most common adverse events (AEs) were elevated AST (87 %) and ALT (77 %), anemia (74 %), hyperglycemia (71 %), and hypercholesterolemia (68 %). Prominent clinical toxicities were mucositis (58 %), weight loss (48 %), and rash (42 %). Most AEs were grade 1 or 2 and largely reversible with infrequent need for everolimus dose reduction. |
| Conclusions: | everolimus plus fulvestrant is effective after AI failure in heavily pretreated metastatic ERpositive breast cancer and has manageable toxicity. Further study of this combination is warranted in randomized studies. Since not all patients experience benefit, and in view of potential toxicities, biomarker examination is critical to help select patients most likely to benefit from this strategy in future studies. |