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

doi:10.1136/esmoopen-2020-000926

ESMO Open

Volume 5, Issue 5, 2020, e000926

https://doi.org/10.1136/esmoopen-2020-000926 Get rights and content

Under a Creative Commons license

open access

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).

ovarian cancer

endometrial cancer

ribociclib

letrozole

Cited by (0)

Presented at: Presented at 2019 American Society of Clinical Oncology Annual Meeting, 2 June 2019, Chicago, Illinois.

Contributors: Conceptualisation: GCO, VZ, NRF, EJA, JAC and SJW. Data curation: GCO, VZ, XH, NRF, EJA and SJW. Formal analysis: GCO, VZ, XH, NRF, EJA and SJW. Funding acquisition: GCO and SJW. Investigation: GCO, VZ, XH, NRF, AEWH, AJ, MSB, CLL, GEC, TAD, MWR, JKC, KAB, JAC and SJW. Methodology: GCO, VZ, XH, EJA and SJW. Project administration: GCO, VZ, XH and SJW. Resources: GCO and SJW. Software: NRF, EJA and SJW. Supervision: GCO, VZ, NRF, EJA, AEWH, AJ, MSB, CLL, GEC, TAD, MWR, JKC, KAB, JAC and SJW. Validation: GCO, VZ, XH, NRF, EJA and SJW. Visualisation: GCO. Writing – original draft: GCO, VZ, XH, NRF, EJA, AEWH, AJ, MSB, CLL, GEC, TAD, MWR, JKC, KAB, JAC and SJW. Writing – review and editing: GCO, VZ, XH, NRF, EJA, AEWH, AJ, MSB, CLL, GEC, TAD, MWR, JKC, KAB, JAC and SJW.

Funding: Funding for this study was provided by Novartis as an Investigator Initiated Trial and by the Mayo Clinic Cancer Center (NCI CA15083).

Competing interests: GC-O and SJW report grants from Novartis during the conduct of the study. MSB reports grants from Immune Design, Pharmacyclics, Marker Therapeutics, Merck, Genentech and Bristol Myers Squibb, outside the submitted work. We certify that the other authors have no financial affiliation/interest (eg, employment, stock holdings, consultant arrangements, honoraria in the subject matter, materials or products) mentioned in this manuscript.

Patient consent for publication: Not required.

Provenance and peer review: Not commissioned; externally peer-reviewed.

Data availability statement: All data relevant to the study are included in the article or uploaded as supplementary information. All relevant data is included in the article.

Author note: Published in abstract form: Colon-Otero G, Weroha SJ, Zanfagnin V, et al. Results of a phase II trial of ribociclib and letrozole in patients with either relapsed estrogen receptor (ER)-positive ovarian cancers or relapsed ER-positive endometrial cancers. J Clin Oncol 2019;37 (suppl):abstr 5510. doi: 10.1200/JCO.2019.37.15_suppl.5510.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.