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Ref Type Journal Article
PMID (27502708)
Authors Dickson MA, Mahoney MR, Tap WD, D'Angelo SP, Keohan ML, Van Tine BA, Agulnik M, Horvath LE, Nair JS, Schwartz GK
Title Phase II study of MLN8237 (Alisertib) in advanced/metastatic sarcoma.
Journal Annals of oncology : official journal of the European Society for Medical Oncology
Vol 27
Issue 10
Date 2016 Oct
URL
Abstract Text Aurora kinase A (AURKA) is commonly overexpressed in sarcoma. The inhibition of AURKA by shRNA or by a specific AURKA inhibitor blocks in vitro proliferation of multiple sarcoma subtypes. MLN8237 (alisertib) is a novel oral adenosine triphosphate-competitive AURKA inhibitor.This Cancer Therapy Evaluation Program-sponsored phase II study of alisertib was conducted through the Alliance for Clinical Trials in Oncology (A091102). Patients were enrolled into histology-defined cohorts: (i) liposarcoma, (ii) leiomyosarcoma, (iii) undifferentiated sarcoma, (iv) malignant peripheral nerve sheath tumor, or (v) other. Treatment was alisertib 50 mg PO b.i.d. d1-d7 every 21 days. The primary end point was response rate; progression-free survival (PFS) was secondary. One response in the first 9 patients expanded enrollment in a cohort to 24 using a Simon two-stage design.Seventy-two patients were enrolled at 24 sites [12 LPS, 10 LMS, 11 US, 10 malignant peripheral nerve sheath tumor (MPNST), 29 Other]. The median age was 55 years; 54% were male; 58%/38%/4% were ECOG PS 0/1/2. One PR expanded enrollment to the second stage in the other sarcoma cohort. The histology-specific cohorts ceased at the first stage. There were two confirmed PRs in the other cohort (both angiosarcoma) and one unconfirmed PR in dedifferentiated chondrosarcoma. Twelve-week PFS was 73% (LPS), 44% (LMS), 36% (US), 60% (MPNST), and 38% (Other). Grade 3-4 adverse events: oral mucositis (12%), anemia (14%), platelet count decreased (14%), leukopenia (22%), and neutropenia (42%).Alisertib was well tolerated. Occasional responses, yet prolonged stable disease, were observed. Although failing to meet the primary RR end point, PFS was promising.NCT01653028.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown angiosarcoma not applicable Alisertib Phase II Actionable In a Phase II trial, Alisertib (MLN8237) treatment resulted in partial response in 2 angiosarcoma patients (PMID: 27502708). 27502708
Unknown unknown sarcoma not applicable Alisertib Phase II Actionable In a Phase II trial, Alisertib (MLN8237) treatment resulted in twelve-week progression free survival in 36% (4/11) of undifferentiated sarcoma patients (PMID: 27502708). 27502708
Unknown unknown liposarcoma not applicable Alisertib Phase II Actionable In a Phase II trial, Alisertib (MLN8237) treatment resulted in twelve-week progression free survival in 73% (9/12) of liposarcoma patients (PMID: 27502708). 27502708
Unknown unknown leiomyosarcoma not applicable Alisertib Phase II Actionable In a Phase II trial, Alisertib (MLN8237) treatment resulted in twelve-week progression free survival in 44% (4/9) of leiomyosarcoma patients (PMID: 27502708). 27502708
Unknown unknown malignant peripheral nerve sheath tumor not applicable Alisertib Phase II Actionable In a Phase II trial, Alisertib (MLN8237) treatment resulted in twelve-week progression free survival in 60% (6/10) of malignant peripheral nerve sheath tumor patients (PMID: 27502708). 27502708
Unknown unknown chondrosarcoma not applicable Alisertib Phase II Actionable In a Phase II trial, Alisertib (MLN8237) treatment resulted in partial response in a dedifferentiated chondrosarcoma patient (PMID: 27502708). 27502708