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Breast Cancer Research
Published in: Breast Cancer Research 2/2014

Open Access 01-04-2014 | Research article

Phase 2 trial of everolimus and carboplatin combination in patients with triple negative metastatic breast cancer

Authors: Jasmeet Chadha Singh, Yelena Novik, Stacey Stein, Matthew Volm, Marlene Meyers, Julia Smith, Coral Omene, James Speyer, Robert Schneider, Komal Jhaveri, Silvia Formenti, Victoria Kyriakou, Benson Joseph, Judith D Goldberg, Xiaochun Li, Sylvia Adams, Amy Tiersten

Published in: Breast Cancer Research | Issue 2/2014

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Abstract

Introduction

Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in breast cancer cell lines. Combination of everolimus also known as RAD001 (oral mammalian target of rapamycin (mTOR) inhibitor) and carboplatin may have activity in metastatic triple-negative breast cancer (TNBC).

Methods

The primary objective of this study was to determine clinical benefit rate (CBR), that is (complete remission (CR) + partial remission (PR) + stable disease (SD) lasting ≥6 months) and the toxicity of everolimus/carboplatin in women with metastatic TNBC. Prior carboplatin was allowed. Treatment consisted of intravenous carboplatin area under the curve (AUC) 6 (later decreased to AUC 5 and subsequently to AUC 4) every 3 weeks with daily 5 mg everolimus.

Results

We enrolled 25 patients in this study. Median age was 58 years. 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%). One SD was achieved in a patient progressing on single agent carboplatin. The median progression free survival (PFS) was 3 months (95% CI 1.6 to 4.6 months) and overall survival (OS) was 16.6 months (95% CI 7.3 months to not reached). There were seven patients (28%) with ≥ 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.

Conclusion

Everolimus-carboplatin was efficacious in metastatic TNBC. Dose limiting hematological toxicity was observed when AUC5/6 of carboplatin was combined with everolimus. However, carboplatin AUC 4 was well tolerated in combination with everolimus with continuing responses.

Trial registrations

ClinicalTrials.gov NCT01127763.
Appendix
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Metadata
Title
Phase 2 trial of everolimus and carboplatin combination in patients with triple negative metastatic breast cancer
Authors
Jasmeet Chadha Singh
Yelena Novik
Stacey Stein
Matthew Volm
Marlene Meyers
Julia Smith
Coral Omene
James Speyer
Robert Schneider
Komal Jhaveri
Silvia Formenti
Victoria Kyriakou
Benson Joseph
Judith D Goldberg
Xiaochun Li
Sylvia Adams
Amy Tiersten
Publication date
01-04-2014
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2014
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3634

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