Phase II study of oral ridaforolimus in women with recurrent or metastatic endometrial cancer

Gynecol Oncol. 2014 Nov;135(2):184-9. doi: 10.1016/j.ygyno.2014.06.033. Epub 2014 Aug 28.


Objective: The phosphatidylinositol-3 kinase/serine-threonine kinase PI3K/AKT pathway is postulated to be central to cancer cell development. Activation of this pathway is believed to promote angiogenesis, protein translation and cell cycle progression. A large percentage of endometrial carcinomas have demonstrated mutations within this regulation pathway which result in constitutional activation. The downstream effector protein mammalian target of rapamycin (mTOR) acts as a critical checkpoint in cancer cell cycling and is a logical target for drug development. The efficacy and tolerability of the oral mTOR inhibitor ridaforolimus were evaluated in this study.

Methods: This phase II study evaluated the single agent tolerability and activity of oral ridaforolimus administered at a dose of 40mg for 5 consecutive days followed by a 2day break, in women with recurrent or metastatic endometrial carcinoma who had received no chemotherapy in the metastatic setting.

Results: 31 of 34 patients were evaluable. Three partial responses (8.8%) were observed with response duration ranging between 7.9 and 26.5months. An additional 18 patients showed disease stabilization (52.9%) for a median duration of 6.6months. Response rates were not affected by previous chemotherapy exposure. No correlation was found between response and mutation status.

Conclusion: Oral ridaforolimus was reasonably tolerated and demonstrated modest activity in women with recurrent or metastatic endometrial cancers. Potential synergy between mTOR inhibition, angiogenesis and hormonal pathways warrants ongoing evaluation.

Keywords: Cancer; Endometrial; Metastatic; Phase II; Recurrent; Ridaforolimus.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Carcinoma, Endometrioid / drug therapy*
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • Treatment Outcome


  • Antineoplastic Agents
  • ridaforolimus
  • TOR Serine-Threonine Kinases
  • Sirolimus