Table 4.

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

Study	Profile	Initial Treatment	Randomization	Primary Endpoint(s)
NCT01953588 ALTERNATE	Phase IIb–III (n: 2820) T2–T4 Allred 6–8	A: Anastrozole B: Fulvestrant C: Fulv + Ana	4/12 weeks Ki67 <10%→ ET ×24 wks Ki67 >10%→ CT ×24 wks  After Surgery PEPI 0→ ET ×5 ys	Modified PEPI + Ki67 at 4/12 wks
NCT00265759 ACOSOG Z1031-B	Phase III (n: 610) Stage II–III Allred 6–8	A: Anastrozole B: Exemestane C: Letrozole	2–4 weeks Ki67 <10% → ET Ki67 >10% → CT or Surgery  After Surgery PEPI 0 → ET alone	ORR pCR for CT arm
NCT01779206ADAPT HR+/HER2–	Phase III (n: 4000) N0-1 and Oncotype RS 12–25	ET	3 weeks Ki67 <10% → ET Ki67 >10% → CT	RFS
NCT02592083 PREDIX-A	Phase II (n: 200) Pre and Post-menopausal Luminal A: ER ≥50% & Ki67 ≤20%	ET	6 weeks Ki67 ≥20%: A: ET ×10 wks B: ET + Palbociclib ×10 wks Ki67 <20%: C: ET + Palbociclib ×10 wks	ORR at 16 wks
NCT02603679 PREDIX-B	Phase II (n: 200) Luminal B or Luminal A (Ki67 >20%) & age <40 or N1	A: Paclitaxel B: ET+ Palbociclib	12 weeks If not progressive disease: A → B ×12 wks B → A ×12 wks	ORR at 24 wks
NCT01613560	Phase II (n: 404) T2-3 ER or PR >50%	ET	16–20 weeks PEPI 0–1 → ET ×5 ys PEPI 2–4 → Randomized to: A: ET ×5 ys B: CT + ET ×5 ys	RFS

ET: Endocrine Therapy; ORR: Overall Response Rate; PD: Progressive Disease; CT: Chemotherapy; RFS: Relapse Free Survival; pCR: Pathologic Complete Response