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

Kosei Hasegawa, Masahiro Kagabu, Mika Mizuno, Katsutoshi Oda, Daisuke Aoki, Seiji Mabuchi, Shoji Kamiura, Satoshi Yamaguchi, Yoichi Aoki, Toshiaki Saito, Mayu Yunokawa, Kazuhiro Takehara, Aikou Okamoto, Kazunori Ochiai, Tadashi Kimura

研究成果: Article査読

19 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)800-812
ページ数13
ジャーナルInvestigational new drugs
35
6
DOI
出版ステータスPublished - 2017 12 1

ASJC Scopus subject areas

  • 腫瘍学
  • 薬理学
  • 薬理学(医学)

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