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Phase II basket trial of perifosine monotherapy for recurrent gynecologic cancer with or without PIK3CA mutations.

Authors :
Hasegawa, Kosei
Kagabu, Masahiro
Mizuno, Mika
Oda, Katsutoshi
Aoki, Daisuke
Mabuchi, Seiji
Kamiura, Shoji
Yamaguchi, Satoshi
Aoki, Yoichi
Saito, Toshiaki
Yunokawa, Mayu
Takehara, Kazuhiro
Okamoto, Aikou
Ochiai, Kazunori
Kimura, Tadashi
Source :
Investigational New Drugs; Dec2017, Vol. 35 Issue 6, p800-812, 13p
Publication Year :
2017

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01676997
Volume :
35
Issue :
6
Database :
Complementary Index
Journal :
Investigational New Drugs
Publication Type :
Academic Journal
Accession number :
126307958
Full Text :
https://doi.org/10.1007/s10637-017-0504-6