| General information |
| Database: | DB01079 |
| Objective: | everolimus and carboplatin combination in patients with triple negative metastatic breast cancer |
| Authors: | Jasmeet Chadha Singh |
| Title: | Phase 2 trial of everolimus and carboplatin combination in patients with triple negative metastatic breast cancer. |
| Journal: | Breast Cancer Research |
| Year: | 2014 |
| PMID: | 24684785 |
| Trial Design |
| Clinical Trial Id: | NCT01127763 |
| 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: | everolimus and carboplatin |
| Study Type: | a singleinstitutionphase II trial. The primary objective of the study was to determine the clinical benefit (CR + PRes + SD lasting more than and equal to 6 months) and toxicity of everolimus and carboplatin combination in women with metastatic TNBC who have had 0 to III prior chemotherapy regimens for metastatic disease. |
| Key Patients Feature: | Eligible patients were women with metastatic histologically confirmed triplenegative breast cancer (ER <10%, PR <10%, HER2neu IHC 0 or 1, or FISHnegative). Additional eligibility criteria included age more than and equal to 18 years; World Health Organization (WHO) performance status less than and equal to 2; adequate bone marrow function (absolute neutrophil count more than and equal to 1. 5¡Á 109/L, platelets more than and equal to 75 ¡Á 109/L, hemoglobin >9 g/dL); adequate liver function (serum bilirubin less than and equal to 1 . 5 ¡Á upper limit of normal (ULN), international normalized ratio (INR) less than and equal to 1 . 5 for patients not on warfarin and INR less than and equal to 3.0 for patients on warfarin, alanine transaminase (ALT) and aspartate transaminase (AST) less than and equal to 2.5 ¡Á ULN (less than and equal to 5 ¡Á ULN in patients with liver metastases)); patients on stable dose of lotheyr molecular weight heparin for >2 weeks at time of treatment; adequate renal function (serum creatinine less than and equal to 1 . 5 ¡Á ULN); fasting serum cholesterol less than and equal to 300 mg/dL or less than and equal to 7 . 75 mmol/L and fasting triglycerides less than and equal to 2 . 5 ¡Á ULN (in case one or both of these thresholds were exceeded, the patient could only be included after initiation of appropriate lipidlotheyring medication); baseline lung computed tomography (CT) scan or positron emission tomography (PET)/CT; oxygen saturation more than and equal to 90% in room air; and negative serum pregnancy test within 7 days prior to starting treatment. Patients could have had 0 to 3 prior regimens for metastatic disease and prior bevacizumabtreated patients were eligible. |
| Biomarker: | triple negative |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | carboplatin was administered with AUC of 4 on day 1 of every cycle, and repeated every 3 weeks. Everolimus was provided by Novartis. The patients were instructed to take 5 mg of everolimus orally once daily continuously from study day 1 until progression of disease or unacceptable toxicity. patients were instructed to take everolimus in the morning, at the same time each day |
| Primary End Point: | to determine clinical benefit rate (CBR), that is (complete remission (CR) + partial remission (PR) + stable disease (SD) lasting more than and equal to 6 months) and the toxicity of everolimus/ carboplatin in women with metastatic TNBC. |
| Secondary End Point: | NA |
| Patients Number: | 25 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | There were one CR, six PRs, seven SDs and eight PDs (progression of disease). CBR was 36% (95% confidence interval (CI) 21.1 to 57.4%) |
| Disease Control Rate: | One SD was achieved in a patient progressing on single agent carboplatin. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median progression free survival (PFS) was 3 months (95% CI 1.6 to 4.6 months) |
| Median OS A vs. C: | overall survival (OS) was 16.6 months (95% CI 7.3 months to not reached) |
| Adverse Event(agent arm): | There were seven patients (28%) with more than and equal to grade 3 thrombocytopenia; three (12%) with grade 3 neutropenia (no bleeding/ febrile neutropenia) and one (4%) with grade 3 anemia. Greater hematological toxicity was seen in the first seven patients treated with carboplatin AUC5/6. After the amendment for starting dose of carboplatin to AUC 4, the regimen was well tolerated with only one out of 18 patients with grade 3 neutropenia and two patients with grade 3 thrombocytopenia. There was only one case of mucositis. |
| Conclusions: | Everolimuscarboplatin was efficacious in metastatic TNBC. Dose limiting hematological toxicity was observed when AUC56 of carboplatin was combined with everolimus. Hotheyver, carboplatin AUC 4 was well tolerated in combination with everolimus with continuing responses. |