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

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This is not medical advice. AI-assisted translation — inaccuracies may occur. Always verify the original and consult your oncologist before taking any steps.

About the trial

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.

Original English text from ClinicalTrials.gov

Who can (and can't) join

✓ Qualifies

  • Kobieta w wieku 19 lat lub więcej
  • Zaawansowany lub rozsiany rak piersi potwierdzony badaniem histologicznym, dodatni na receptory hormonalne, ujemny na HER2, nie do operacyjnego leczenia
  • Brak wcześniejszego leczenia chemią lub hormonami na zaawansowanego raka piersi
  • Jeśli pacjent otrzymywał inhibitory aromatazy, okres bez leczenia powinien trwać ponad 12 miesięcy; dla tamoksyfenu okres może być krótszy
  • Ogólny stan zdrowia oceniony na 0-2 w skali ECOG
  • Widoczne lub mierzalne zmiany nowotworowe
  • Odpowiednia funkcja narządów: liczba neutrofili ≥1,5, płytki ≥100, hemoglobina ≥9, prawidłowe wartości wątroby i nerek
  • Kobiety w wieku rozrodczym muszą stosować skuteczną antykoncepcję przez badanie i 6 miesięcy po jego zakończeniu

✗ Disqualifies

  • Wcześniejsze leczenie inhibitorami CDK4/6 lub inną terapią zaawansowanego raka piersi
  • Wcześniejsze leczenie fulwestrantem lub innymi lekami ukierunkowanymi na receptor estrogenowy
  • Nawrót choroby podczas leczenia inhibitorami aromatazy
  • Przerzuty do mózgu objawowe lub nieleczone
  • Historia choroby serca lub zawału mięśnia sercowego w ostatnich 6 miesięcy
  • Szybko postępująca choroba wymagająca natychmiastowego zmniejszenia guza
  • Historia innego nowotworu złośliwego (poza czerniakiem skóry, rakiem in-situ szyjki macicy, rakiem tarczycy)
  • Aktywna infekcja wirusem hepatitis B lub C, HIV, lub zaburzenia odporności

Simplified criteria — AI translation

Trial details

Minimum age
19 Years
Maximum age
80 Years
Last updated (source)
March 18, 2025
Sex
Female only

Therapies / drugs in trial

Locations (2)

Korea university Guro hospital

Seoul, South Korea

St Mary Hospital

Seoul, South Korea

Trial contact

Contact information from ClinicalTrials.gov. Contact in English.

Share this trial

Data from ClinicalTrials.gov. AI-assisted translation, last sync: 7/1/2026.

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