Phase II trial of ribociclib and letrozole in patients with relapsed oestrogen receptor-positive ovarian or endometrial cancers

Gerardo Colon-Otero, Valentina Zanfagnin, Xiaonan Hou, Nathan R. Foster, Erik J. Asmus, Andrea Wahner Hendrickson, Aminah Jatoi, Matthew S. Block, Carrie L. Langstraat, Gretchen E. Glaser, Tri A. Dinh, Matthew W. Robertson, John K. Camoriano, Kristina A. Butler, John A. Copland, S. John Weroha

Research output: Contribution to journalArticlepeer-review

Abstract

Objective We describe a phase II clinical trial of the combination of ribociclib and letrozole for treatment of relapsed oestrogen receptor (ER)-positive ovarian cancer (OC) and endometrial cancer (EC). The primary endpoint was the proportion of patients alive, progression-free survival (PFS), and still on treatment at 12 weeks (PFS12), with 45% or greater considered positive. Methods Patients with measurable, relapsed ER-positive OC or EC (platinum-sensitive or resistant) were eligible and treated with 400 mg of oral ribociclib and 2.5 mg of oral letrozole daily. Patient-derived xenografts (PDXs) were created from imaging-guided tumour biopsies. Results Forty patients (20 OC and 20 EC) were enrolled. A PFS12 of 55% was observed in the EC cohort and 50% in the OC cohort. A PFS greater or equal to 24 weeks (PFS24) was seen in 20% (4/20) of the OC cohort and 35% (7/20) of the EC cohort. The greatest benefit was seen in low-grade serous OC (LGSOC) (3/3, 100% PFS24) and grades 1 and 2 EC (5/11, 45% PFS24). All three LGSOC patients obtained at least a partial response lasting for over 2 years, with two of the three patients still on treatment. PDX tumour engraftment was feasible in 45% of patients. Positive survival effects of the combination of ribociclib and letrozole were observed in two of three EC PDX models. Conclusion Ribociclib and letrozole have promising clinical activity in relapsed ER-positive OC and EC, particularly in LGSOC and relapsed ER-positive grade 1 and 2 EC. Generation of PDX models is feasible with positive survival effects observed in EC models.

Original languageEnglish (US)
Article numbere000926
JournalESMO Open
Volume5
Issue number5
DOIs
StatePublished - Oct 27 2020

Keywords

  • endometrial cancer
  • letrozole
  • ovarian cancer
  • ribociclib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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