Table 3.

The trials evaluating CDK4/6 inhibitors in the adjuvant setting of HR+/HER2- breast cancer. iDFS was the primary endpoint in all studies mentioned in the table.

Trial acronym, NCT number	Main inclusion criteria	Number of randomized patients	Intervention arm	iDFS benefit	Median follow-up time	EMA and FDA approval
MonarchE, NCT03155997 [85]	Cohort 1: ≥ 4 ALN OR 1–3 ALN with grade 3 and/or tumor size ≥ 5 cm Cohort 2: 1–3 ALN and Ki-67 ≥ 20% (grade 1–2 and/or tumor size ≤ 5 cm)	5,637	Abemaciclib 150 mg twice daily for 2 years with SOC endocrine therapy	HR 0.67 (95% CI 0.59–0.76)	54 months	Approved (cohort 2 only by FDA)
NATALEE, NCT03701334 [86]	Stage II with high-risk features or stage III	5,101	Ribociclib 400 mg once daily days 1–21 of a 28-day cycle for 3 years with SOC endocrine therapy	HR 0.75 (95% CI 0.63-0.89)	33.3 months	Approved
PALLAS, NCT02513394 [84]	Stage II or III	5,796	Palbociclib 125 mg daily days 1–21 of a 28-day cycle for 2 years with SOC endocrine therapy	HR 0.96 (95% CI 0.81–1.14)	31 months	Not approved
PENELOPE-B, NCT01864746 [83]	Residual disease at surgery, with CPS-EG score ≥ 3 or 2 with ypN+	1,250	Palbociclib 125 mg daily days 1–21 of a 28-day cycle for 1 year with SOC endocrine therapy	HR 0.93 (95% CI 0.74–1.17)	42.8 months	Not approved

ALN: axillary lymph node; CI: confidence interval; CPS-EG: clinical pathological staging-estrogen receptor grading; HR: hazard ratio; iDFS: invasive disease-free survival; NCT: National Clinical Trial; SOC: standard of care; HER2: human epidermal growth factor receptor 2.