Prospective Single-Arm Study of Endocrine Therapies With Ovarian Function Suppression in Premenopausal Node-Positive Early Breast Cancer Patients With Low Genomic Risk (INTERSTELLAR Trial, KBCSG-25)

Abstract

Purpose: While postmenopausal women with low recurrence scores in genomic assay may safely forgo adjuvant chemotherapy, the RxPONDER trial demonstrated that premenopausal women with 1-3 positive nodes (pN1) derive significant benefit from adjuvant chemotherapy regardless of low recurrence scores. The INTERSTELLAR trial is evaluating whether ovarian function suppression (OFS) combined with adjuvant endocrine therapy (ET) can offer comparable efficacy to chemotherapy in this specific patient population. Methods: INTERSTELLAR is a prospective, multicenter, single-arm, non-inferiority cohort study enrolling premenopausal women aged <= 50 with pT1-2, estrogen receptor +/human epidermal growth factor receptor 2-, pN1 breast cancer. Genomic risk is assessed using OncoFREE (R), a next-generation sequencing-based assay developed in the Republic of Korea. Patients classified as low genomic risk (Decision Index <= 20) receive OFS combined with either an aromatase inhibitor or tamoxifen for 5 years, while patients with high genomic risk receive standard adjuvant chemotherapy followed by ET. The primary endpoint is 5-year distant disease-free survival (DDFS). Non-inferiority will be established if the lower bound of the 97.5% one-sided confidence interval exceeds 93.1%, benchmarked against a historical control DDFS of 96.1% derived from the RxPONDER trial. The study plans to enroll 604 patients total, with a target of 380 evaluable low-risk patients after accounting for expected genomic risk distribution and study dropout rates. Discussion: Our results may establish evidence supporting the omission of adjuvant chemotherapy in premenopausal women with low genomic risk scores and limited nodal involvement (p-N1), potentially reducing treatment-related morbidity while preserving comparable oncologic outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT05333328. Registered on April 18, 2022.