Endocrine Maintenance Therapy in High-Grade Serous Ovarian Cancer: A Retrospective Off-Label Real-World Cohort Study
by
, , ,
Franziska Geissler
1,2,†
,
Flurina Graf
3,†,
Tibor A. Zwimpfer
1,2,
Ruth S. Eller
1,2,
Bich Doan Nguyen-Sträuli
1,
Andreas Schötzau
1,
Viola Heinzelmann-Schwarz
1,2,* and
Ursula Gobrecht-Keller
1 1
Gynaecological Cancer Centre, University Hospital Basel, 4031 Basel, Switzerland
2
Ovarian Cancer Research, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland
3
Medical Faculty, University of Basel, 4031 Basel, Switzerland
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2025, 17(8), 1301; https://doi.org/10.3390/cancers17081301
Submission received: 9 March 2025
/
Revised: 6 April 2025
/
Accepted: 10 April 2025
/
Published: 12 April 2025
(This article belongs to the Special Issue Gynecological Cancer: Prevention, Diagnosis, Prognosis and Treatment)
Simple Summary
Endocrine therapy is used for decades as a standard in the maintenance therapy in estrogen receptor positive breast cancer and now frequently discussed in low-grade serous ovarian cancers. For high-grade serous ovarian cancers only limited data in heavily pretreated patients is available. Thus, this study investigates endocrine therapy with the aromatase inhibitor letrozole alone or in combination with established targeted therapies in the maintenance after first line treatment with cytoreductive surgery and adjuvant chemotherapy in high-grade serous ovarian cancer patients. Our study demonstrates a good safety profile and thus feasibility for aromatase inhibitor letrozole in this setting. Moreover, Letrozole maintenance therapy shows a potential survival benefit in a selected group of high-grade serous ovarian cancer patients without residual disease after primary surgery. These findings highlight the potential of endocrine therapy as a well-tolerated option in high-grade serous ovarian cancers patients and the need for further validation through prospective randomized clinical trials to comprehensively assess its efficacy and its implications for patient quality of life.
Abstract
Background: Endocrine therapy is the standard-of-care maintenance treatment for estrogen receptor (ER)-positive breast cancers and is increasingly used in low-grade serous ovarian cancer. However, its therapeutic role in the early maintenance setting for ER-positive high-grade serous ovarian cancer (HGSC) remains undefined. Methods: A retrospective analysis was conducted on clinicopathological data from patients with newly diagnosed ER-positive HGSC following completion of adjuvant chemotherapy. Patients received maintenance therapy either with or without the aromatase inhibitor letrozole, in addition to standard maintenance care. ER expression levels and the administration of letrozole were analyzed, along with outcome measures for the entire cohort, with stratification based on residual disease status. Results: A total of 102 patients with newly diagnosed HGSC were included in the analysis, with 64 (62.7%) receiving letrozole and 38 (37.3%) not receiving letrozole. The median ER expression was 70%, with higher expression observed in the letrozole group compared to the no letrozole group (77.5% vs. 60%). No significant correlation was found between ER expression status and therapy response (p = 0.295 and p = 0.176, respectively). Letrozole therapy was well tolerated with no major adverse effects reported. In the overall cohort, maintenance letrozole therapy did not confer a significant improvement in progression-free survival (median 20.56 months vs. 29.34 months, p = 0.53) or overall survival (OS) (median 79.48 months vs. 46.85 months, p = 0.71) over a median follow-up duration of 23.5 months. However, among patients with no residual disease, maintenance letrozole therapy was associated with a statistically significant improvement in OS compared to those not receiving letrozole (median 114 months vs. 46.9 months, p = 0.006). Conclusions: Maintenance letrozole therapy appears to be a well-tolerated and potentially beneficial intervention in a subset of patients with ER-positive HGSC with no residual disease post-treatment. These findings highlight the need for further validation through prospective randomized trials to comprehensively assess the efficacy of endocrine therapy in this setting and its implications for patient quality of life.
