Comparison of Clinical Efficacy Between Letrozole + Ribociclib and Fulvestrant + Letrozole + Ribociclib in Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer

Last updated: March 13, 2025
Sponsor: Korea University Guro Hospital
Overall Status: Active - Recruiting

Phase

2

Condition

Breast Cancer

Metastatic Cancer

Treatment

Fulvestrant plus AI plus ribociclib

AI plus ribociclib

Clinical Study ID

NCT05816655
KCSG BR22-20
  • Ages 19-80
  • Female

Study Summary

Aromatase inhibitor (AI) + CDK4/6 inhibitor is settled down as the standard first line therapy for HR+/HER2- metastatic breast cancer and all three CDk4/6 inhibitors, palbociclib, ribociclib, and abemaciclib are currently available for same indications. However, there is no effective treatment strategy for patients who have progressed on AI+CDK4/6 inhibitor. In particular, the clinical efficacies of subsequent hormone therapy are lowered when ESR1 mutations, one of mechanisms of AI resistance occur. In the PADA-1 trial, when ESR1 mutations in ctDNA were detected in patients treated with AI+CDK4/6 inhibitor, AI was switched to fulvestrant even if disease progression was not confirmed clinically. As a result, the median PFS was prolonged by about 8 months in this switching group compared to the group in which AI was continued. The results of this study suggested that delaying the occurrence of ESR1 mutations and early response to them are necessary to increase the effectiveness of hormone therapy.

In SWOG S0226 study, fulvestrant + AI combination showed significant benefits in PFS and OS compared to AI monotherapy as the first line therapy. Based on these results, the NCCN guideline suggests fulvestrant + AI combination as one of the first line hormone therapy options. However, the clinical effect of AI + fulvestrant + CDK4/6 inhibitor has not been investigated yet. Therefore, the investigators are planning to compare the clinical efficacy of AI+ fulvestrant + CDK4/6 inhibitor and AI+CDK4/6 inhibitor, and to investigate if a triple combination regimen can delay the emergence of ESR1 mutations and modulate occurred ESR1 mutations.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Female ≥ 19 years of age

  • Histologically confirmed unresectable, locally advanced or metastatic invasivebreast cancer with hormone receptor positive/HER2 negative

  • No previous history of systemic endocrine or chemotherapy for metastatic, advancedbreast cancer.

  • If the patient has received AI as adjuvant endocrine therapy, the treatment freeinterval (TFI) should be more than 12 months after the end of adjuvant endocrinetherapy. If the patient has received tamoxifen for adjuvant endocrine therapy, TFIless than 12 months will be allowed.

  • ECOG PS 0-2

  • Patients should have measurable or evaluable lesion based on RECIST version 1.1

  • Patients should have adequate organ function:

  • ANC (absolute neutrophil count) ≥ 1.5 × 109/L

  • Platelet ≥ 100 × 109/L

  • Serum Hb ≥ 9.0 g/dL

  • INR ≤1.5

  • Serum creatinine ≤ 1.5 X ULN

  • ALT & ALT <2.5 X ULN, if patients have hepatic metastasis, ALT & ALT <5.0 X ULNis allowed

  • Total serum bilirubin <1.5 X ULN, if patients have hepatic metastasis, Totalserum bilirubin <3.0 X ULN is allowed.

  • In the case of childbearing potential, patients who can adhere to appropriatecontraception during the study period and for at least 6 months after the end ofstudy treatment.

  • Patients who understand the contents of the clinical trial and are cooperative withthe process of the clinical trial.

Exclusion

Exclusion Criteria:

  • Patients with a history of previous treatment with a CDK4/6 inhibitor or othersystemic treatment for advanced/metastatic breast cancer

  • Patients who have received prior treatment with fulvestrant and any investigationalER-directed therapy including SERDs (selective estrogen receptor degrader)

  • Patients who have disease recurrence on aromatase inhibitor treatment as adjuvantendocrine therapy

  • Patients who have symptomatic or untreated central nervous system metastasis

  • Patients who have a history of cardiovascular disease or heart failure as followingconditions; within at least 6 months of myocardial infarction, unstable angina, oruncontrolled arrhythmia.

  • Patients having visceral crisis which needs rapid tumor reduction

  • Patients who have a history of any other cancer (except nonmelanoma skin cancer,carcinoma in-situ of the cervix, well-differentiated thyroid cancer)

  • Patients unable to cooperate with periodic blood samples collection

  • Patients who have active HBV, HCV infection, immune-suppressive disease, or HIVinfection. In case of chronic HBV infection, HBV DNA should be negative. Patientswith complete remission of HCV infection are allowed.

  • Pregnant or breast-feeding women

  • Patients who are considered to be unsuitable for this trial by investigators.

Study Design

Total Participants: 202
Treatment Group(s): 2
Primary Treatment: Fulvestrant plus AI plus ribociclib
Phase: 2
Study Start date:
May 31, 2023
Estimated Completion Date:
June 30, 2029

Connect with a study center

  • Korea university Guro hospital

    Seoul,
    Korea, Republic of

    Active - Recruiting

  • St Mary Hospital

    Seoul,
    Korea, Republic of

    Active - Recruiting

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