Phase II trial of ribociclib and letrozole in patients with relapsed oestrogen receptor-positive ovarian or endometrial cancers. Issue 5 (27th October 2020)

• Record Type: Journal Article
• Authors: Colon-Otero, Gerardo; Zanfagnin, Valentina; Hou, Xiaonan; Foster, Nathan R; Asmus, Erik J; Wahner Hendrickson, Andrea; Jatoi, Aminah; Block, Matthew S; Langstraat, Carrie L; Glaser, Gretchen E; Dinh, Tri A; Robertson, Matthew W; Camoriano, John K; Butler, Kristina A; Copland, John A; Weroha, S John
• Is Part Of: ESMO open. Volume 5:Issue 5(2020)
• Publication Date: 2020-10-27
• Subjects: ovarian cancer -- endometrial cancer -- ribociclib -- letrozole; Cancer -- Periodicals; 616.994005
• DOI: 10.1136/esmoopen-2020-000926
• Languages: English
• ISSNs: 2059-7029

Abstract

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. Trial registration number: ClinicalTrials.gov registry (NCT02657928 ).