# Efficacy and Safety of Chemotherapy Combined with Hormonal Therapy in Heavily Pretreated Advanced Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ELSA/KGOG3049): A Multicenter Pilot Study

## TL;DR

This study explores combining chemotherapy with hormone therapy in advanced ovarian cancer patients who have had multiple prior treatments, finding potential benefits in those with estrogen receptor dominance.

## Contribution

The study introduces a personalized approach combining chemotherapy with hormone therapy based on hormone receptor expression in heavily pretreated ovarian cancer patients.

## Key findings

- Chemotherapy combined with tamoxifen showed a 27.3% six-month objective response rate in estrogen receptor-dominant patients.
- No significant clinical response was observed in progesterone receptor-dominant patients.
- The treatment was well-tolerated with no unacceptable toxicity.

## Abstract

Many patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer experience recurrence after the initial treatment, and the effectiveness of chemotherapy decreases with each recurrence. Therefore, new strategies are urgently needed to improve outcomes in patients who have already undergone multiple lines of treatment. Hormonal therapy has been used for ovarian cancer, but its role when combined with chemotherapy and tailored to hormone receptor expression is unclear. This study examined whether combining chemotherapy with hormonal therapy could improve clinical outcomes in patients with heavily pretreated cancer. Patients whose tumors had more estrogen receptors received tamoxifen, while those with more progesterone receptors received megestrol acetate, each combined with chemotherapy. These findings suggest that the combination of tamoxifen and chemotherapy may provide potential clinical benefit and manageable safety in selected patients. These exploratory results support a further investigation of a personalized approach based on hormone receptor status in late-line ovarian cancer therapy.

Background/Objectives: The effects of combining chemotherapy with hormonal therapy based on hormone receptor (HR) expression in epithelial ovarian, fallopian tube, or primary peritoneal (EOC) remain unclear. This study evaluated the efficacy and safety of physician-chosen chemotherapy combined with hormonal therapy in patients with heavily pretreated advanced EOC, stratified by HR expression. Methods: This phase II, multicenter, pilot study included patients with heavily pretreated advanced EOC, allocated to estrogen receptor (ER)-dominant or progesterone receptor (PR)-dominant arms. Patients in the ER-dominant arm received tamoxifen plus physician-selected chemotherapy, while those in the PR-dominant arm received megestrol acetate (MA) plus chemotherapy. The primary outcome was the best objective response rate (ORR) for six months, assessed using an optimal two-stage Simon design. Results: Among 33 ER-dominant patients with high-grade serous carcinoma (HGSC), the six-month best ORR was 27.3% (3% complete response, 24.2% partial response). The six-month ORR and clinical benefit rate (CBR) were 18.8% and 37.5%, respectively, with 62.5% experiencing progressive disease (PD). Among three PR-dominant patients (two clear cell carcinoma and one HGSC), the six-month best ORR was 0%. The six-month ORR and CBR were also 0%, and all experienced PD within six months. No unacceptable toxicity related to tamoxifen or MA was encountered. Conclusions: In heavily pretreated advanced HGSC patients with ER-dominant expression, chemotherapy combined with tamoxifen showed encouraging clinical activity with favorable safety. While limited by the study design, these findings suggest a potential role for tailored hormonal therapy combined with chemotherapy based on HR expression in heavily pretreated advanced EOC. Clinical Trial Registration: KCT0004571