Table 2.

Trials for CDK4/6 Inhibitors in HR+/HER2- Early Breast Cancer.

	PALLAS85	PENELOPE-B86	monarchE87	NATALEE88
Study Design
Sponsor/Collaborator	ABCSG/AFT	GBG	Eli Lilly/NSABP	Novartis/TRIO
NCT#	NCT02513394	NCT01864746	NCT03155997	NCT03701334
Design	Phase 3	Phase 3	Phase 3	Phase 3
	Randomized	Randomized	Randomized	Randomized
	Open label	Placebo-controlled	Open label	Open label
Sample size	5796	1250	5637	5101
Treatment arms	Palbociclib 125 mg QD, 3/1 schedule (2 years) + SOC ET vs. SOC ET	Palbociclib 125 mg QD, 3/1 schedule (1 year) + SOC ET vs. Placebo QD, 3/1 schedule (1 year) + SOC ET	Abemaciclib 150 mg BID (2 years) + SOC ET vs. SOC ET	Ribociclib 400 mg QD, 3/1 schedule (3 years) + SOC ET vs. SOC ET
Target population	Stage II/III (Stage IIA capped at 1000 pts)	Residual disease and an increased risk of recurrence after neoadjuvant chemotherapy	High-risk disease defined as lymph node + plus one other risk factor	Stage II/III
Key inclusion criteria	• ≤ 12 months since initial pathologic diagnosis • ≤ 6 months from first dose of SOC adj. ET if started • Prior chemotherapy (CTx) allowed	• ≤ 16 weeks of neoadjuvant CTx including at least 6 weeks of taxane-containing regimen • Residual invasive disease in breast or LN post-neoadjuvant therapy • CPS-EG scorea ≥ 3 or 2 if nodal status at surgery is ypN+	• Pathologic lymph node involvement + at least one of the following: ▪ ≥ 4 (+) axillary LN ▪ ≥ 5 cm tumor ▪ Grade 3 ▪ Ki-67 ≥ 20% on untreated breast tissue by central analysis • ≤ 16 months since definitive surgery • ≤ 12 weeks of ET until randomization following last non-ET (surgery, CTx, or radiation) whichever is last • Prior CTx allowed	• Definitive breast surgery for the current malignancy with/without Rx • Prior CTx allowed

^aThe CPS+EG score estimates relapse probability on the basis of clinical and pathologic stage (CPS) and estrogen receptor status and histologic grade (EG). Scores range from 0 to 6, with higher scores indicating higher risk of relapse⁸⁹. ABCSG/AFT Austrian Breast & Colorectal Cancer Study Group/Alliance Foundation Trials, BID Two times a day, CPS-EG Clinical-Pathologic Scoring System incorporating estrogen receptor status and nuclear grade, CTx Chemotherapy, ET Endocrine therapy, GBG Global Benefits Group, HER2 Human epidermal growth factor receptor 2, HR Hormone receptor, LN Lymph node, LPFV Last patient, first visit, NCT National Clinical Trial, NSABP National Surgical Adjuvant Breast and Bowel Project, QD Every day, SOC Standard of care.