Table 4.

Randomized clinical trials investigating the clinical utility of Ki67 and PEPI scores

StudyProfileInitial treatmentRandomizationPrimary endpoint(s)
NCT01953588Phase IIb–III (n = 2820)A: Anastrozole4/12 weeksModified PEPI + Ki67 at 4/12 weeks
ALTERNATET2–T4B: FulvestrantKi67 <10% → ET × 24 weeks
Allred 6–8C: Fulvestrant + anastrozoleKi67 >10% → CT × 24 weeks
After surgery
PEPI 0 → ET × 5 years
NCT00265759Phase III (n = 610)A: Anastrozole2–4 weeksORR
ACOSOG Z1031-BStage II–IIIB: ExemestaneKi67 <10% → ETpCR for CT arm
Allred 6–8C: LetrozoleKi67 >10% → CT or surgery
After surgery
PEPI 0 → ET alone
NCT01779206Phase III (n = 4,000)ET3 weeksRFS
ADAPT HR+/HER2N0-1 and Oncotype RS 12–25Ki67 <10% → ET
Ki67 >10% → CT
NCT02592083Phase II (n = 200)ET4 weeksORR at 16 weeks
PREDIX-APre- and postmenopausal

Ki67 decrease ≥20%:

  •  A: ET × 10 weeks

  •  B: ET + palbociclib × 10 weeks

Luminal A: ER ≥50% and Ki67 ≤20%

Ki67 decrease <20%:

  •  C: ET + palbociclib ×  10 weeks

NCT02603679Phase II (n = 200)A: Paclitaxel12 weeksORR at 24 weeks
PREDIX-BLuminal B or Luminal A (Ki67 >20%) and age <40 years or N1B: ET + palbociclib

If not progressive disease:

  • A → B × 12 weeks

  • B → A × 12 weeks

NCT01613560Phase II (n = 404)ET16–20 weeksRFS
T2–3PEPI 0–1 → ET × 5 years
ER or PR >50%

PEPI 2–4 → randomized to:

  • A: ET × 5 years

  • B: CT + ET × 5 years

  • Abbreviations: CT, chemotherapy; ET, endocrine therapy,