TY - JOUR
T1 - Phase II basket trial of perifosine monotherapy for recurrent gynecologic cancer with or without PIK3CA mutations
AU - Hasegawa, Kosei
AU - Kagabu, Masahiro
AU - Mizuno, Mika
AU - Oda, Katsutoshi
AU - Aoki, Daisuke
AU - Mabuchi, Seiji
AU - Kamiura, Shoji
AU - Yamaguchi, Satoshi
AU - Aoki, Yoichi
AU - Saito, Toshiaki
AU - Yunokawa, Mayu
AU - Takehara, Kazuhiro
AU - Okamoto, Aikou
AU - Ochiai, Kazunori
AU - Kimura, Tadashi
N1 - Funding Information:
This trial was supported by Yakult Honsha Co., Ltd. We would like to thank all patients, clinicians, and support staff who participated in this trial. We are grateful to Ichinosuke Hyodo and Fumitaka Nagamura for their helpful advice as members of the data monitoring committee. We also thank Atsushi Takamine and Takeshi Mimura for their helpful advice. This work was sponsored by Yakult Honsha Co., Ltd.
Publisher Copyright:
© 2017, Springer Science+Business Media, LLC.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
KW - Cervical cancer
KW - Endometrial cancer
KW - Ovarian cancer
KW - PIK3CA
KW - Perifosine
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U2 - 10.1007/s10637-017-0504-6
DO - 10.1007/s10637-017-0504-6
M3 - Article
C2 - 28864978
AN - SCOPUS:85028751601
SN - 0167-6997
VL - 35
SP - 800
EP - 812
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 6
ER -
