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Ref Type Journal Article
PMID (28864978)
Authors Hasegawa K, Kagabu M, Mizuno M, Oda K, Aoki D, Mabuchi S, Kamiura S, Yamaguchi S, Aoki Y, Saito T, Yunokawa M, Takehara K, Okamoto A, Ochiai K, Kimura T
Title Phase II basket trial of perifosine monotherapy for recurrent gynecologic cancer with or without PIK3CA mutations.
Journal Investigational new drugs
Vol 35
Issue 6
Date 2017 12
URL
Abstract Text Objective Perifosine exhibits anti-tumor activity by inhibiting AKT phosphorylation. The purpose of this phase II basket trial was to evaluate the efficacy and safety of perifosine monotherapy for ovarian, endometrial, and cervical cancers. Methods Recurrent or persistent ovarian, endometrial, or cervical cancer patients were assigned to PIK3CA wild-type or mutant groups. Each patient received 600 mg oral perifosine on day 1 followed by a maintenance dose of 100 mg daily. The primary endpoint was disease control rate; secondary endpoints included response rate, progression-free survival, overall survival, and safety. Immunohistochemical staining and targeted sequencing were used to explore new biomarkers in such patients. Results Sixteen and 5 ovarian, 17 and 7 endometrial, and 18 and 8 cervical cancer patients with PIK3CA wild-type and mutant, respectively, were enrolled. Disease control rates (wild-type/mutant) were 12.5/40.0%, 47.1/14.3%, and 11.1/25.0% in ovarian, endometrial, and cervical cancer, respectively. The most common grade 3/4 toxicities were anemia (22.5%) and anorexia (11.3%). Immunohistochemical staining revealed that the disease control rate in patients with negative phosphatase and tensin homolog (PTEN) expression was 50.0%, and the odds ratio of positive to negative patients was 0.24 in all patients. Conclusions Perifosine monotherapy showed good tolerability but expected efficacy was not achieved. Modest efficacy was demonstrated in ovarian cancer patients with PIK3CA mutations and endometrial cancer patients with PIK3CA wild-type; no difference was observed between PIK3CA wild-type and mutant in cervical cancer. Absence of PTEN expression may be predictive of clinical efficacy with perifosine monotherapy.

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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
Perifosine KRX-0401|NSC-639966 Akt Inhibitor (Pan) 18 Perifosine (KRX-0401) is a synthetic alkylphospholipid that inhibits AKT resulting in apoptotic induction and antitumor activity (PMID: 16418332, PMID: 28864978, PMID: 31325145).
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
PIK3CA mutant ovarian cancer not predictive Perifosine Phase II Actionable In a Phase II trial , Perifosine (KRX-0401) treatment was well-tolerated, resulted in stable disease as best response in patients with recurrent ovarian cancer, no significant difference in disease control rate (12.5%, 2/16 vs 40%, 2/5, p=0.22), median progression-free survival (HR=0.57, p=0.32), or median overall survival (HR=1.37, p=0.58) was identified between PIK3CA wild-type and PIK3CA mutant patients (PMID: 28864978). 28864978
PIK3CA mutant cervical cancer not predictive Perifosine Phase II Actionable In a Phase II trial , Perifosine (KRX-0401) treatment was well-tolerated, resulted in stable disease as best response in patients with recurrent cervical cancer, no significant difference in disease control rate (11.1%, 2/18 vs 25%, 2/8, p=0.56), median progression-free survival (HR=1.06, p=0.81), or median overall survival (HR=1.66, p=0.26) was identified between PIK3CA wild-type and PIK3CA mutant patients (PMID: 28864978). 28864978
PIK3CA mutant endometrial cancer not predictive Perifosine Phase II Actionable In a Phase II trial , Perifosine (KRX-0401) treatment was well-tolerated, resulted in stable disease as best response in patients with recurrent endometrial cancer, no significant difference in disease control rate (47.1%, 8/17 vs 14.3%, 1/7, p=0.19), median progression-free survival (HR=1.71, p=0.30), or median overall survival (HR=0.92, p=0.88) was identified between PIK3CA wild-type and PIK3CA mutant patients (PMID: 28864978). 28864978