309P - Expression of estrogen receptor is a negative predictive biomarker for immunotherapy with lenvatinib plus pembrolizumab for advanced endometrial cancer with pMMR

Background

Immunotherapy with lenvatinib plus pembrolizumab (LP) prolonged progression-free survival (PFS) and overall survival (OS) in patients with advanced endometrial cancer. However, the predictive biomarker for this therapy is still unclear. Some studies on breast and prostate cancer have suggested that expression of hormone receptors (HRs) has immune regulatory functions. Therefore, we explored whether the HRs expression could be a predictive biomarker of LP therapy.

Methods

We retrospectively reviewed clinicopathological information on patients with advanced mismatch repair proficient (pMMR) endometrial cancer who underwent LP therapy between January 2022 and March 2023 at the National Cancer Center Hospital. Expression of HRs was evaluated for estrogen receptor (ER) and progesterone receptor (PR) by immunohistochemistry. Cases were dichotomized, using 10% as a cut-off value. Expression of p53 and programmed cell death ligand-1 (PD-L1) were also confirmed. PFS and OS were compared according to the status of HRs, p53, and PD-L1 expressions by log-rank test. Multivariate analysis using Cox proportional hazard model was performed to confirm the prognosis factor.

Results

A total of 19 patients were reviewed, including four patients with carcinosarcoma. Twelve patients were ER-positive and 11 were PR-positive. Thirteen had an aberrant type of p53 expression and, 14 had PD-L1 positive (combined positive score ≥ 1). No association was found between prognosis and expression status of PR, p53, or PD-L1. However, patients with ER-positive had a significantly poorer PFS (4.3 vs. 10.0 months, hazard ratio [HR]: 3.28, p = 0.038) than those with ER-negative. Multivariate analysis confirmed that ER-positive is a statistically poor prognostic factor for PFS. Similarly, ER-positive patients tended to have a poorer OS (6.2 vs. 11.5 months, HR: 1.92, p = 0.375) than ER-negative patients. Overall response rate was 42% and 71% for ER-positive and negative patients, respectively.

Conclusions

ER expression was associated with shorter PFS of LP therapy. ER expression in tumors was a negative predictive biomarker in LP therapy for advanced endometrial cancer with pMMR.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Nishikawa: Financial Interests, Personal, Invited Speaker: MSD, Eisai. All other authors have declared no conflicts of interest.