Ribociclib in the Treatment of Hormone-Receptor Positive/HER2-Negative Advanced and Early Breast Cancer: Overview of Clinical Data and Patients Selection

Figures & data

Table 1 Phase 3 Ribociclib Studies in Advanced Breast Cancer

Author/Year	Patients	Treatment	Results	Subgroup Analysis of OS (HR, 95% CI)	Subgroup Analysis of PFS (HR, 95% CI)
Slamon et al^Citation1 MONALEESA-3	Postmenopausal HR+/HER2- advanced BC/0-1 prior endocrine tx for advanced BC (n=726)	● RIBO 600 mg/die, 21 days on/7 days off + FULV 500 mg im q 28d (n=484) ● PLAC + FULV 500 mg im q 28d (n=242)	Median PFS 20.5 vs 12.8 months (HR=0.59; 95% CI Median follow up 56.3 months: Median OS: 53.7 vs 41.5 months (HR=0.73; 95% CI 0.59–0.90) ORR: 32.4 vs 21.5% CBR: 70.2 vs 62.8%	Line of therapy: first vs second line ● 0.64 (0.46–0.88) vs 0.78 (0.59 1.04) Bone only metastases: yes vs no ● 0.67 (0.42–1.08) vs 0.74 (0.58–0.93) Visceral involvement: yes vs no ● 0.73 (0.55–0.98) vs 0.74 (0.54–1.01) Prior endocrine therapy: naïve vs resistance vs sensitive ● 0.62 (0.41–0.95) vs 0.82 (0.45–1.47) vs 0.73 (0.56–0.96)	Line of therapy: naïve vs second line ● 0.57 (0.41–0.8) vs 0.56 (0.42–0.74) Bone only metastases: yes vs no ● 0.37 (0.23–0.61) vs 0.65 (0.51–0.83) Visceral involvement: yes vs no ● 0.64 (0.48–0.86) vs 0.56 (0.41–0.76) Prior aromatase inhibitors: yes vs no ● 0.67 (0.5–0.88) vs 0.48 (0.34–0.66)
Hortobagyi et al^Citation2,Citation5,Citation7,Citation8 MONALEESA-2	Postmenopausal HR+/HER2 – recurrent/metastatic BC, no prior systemic therapy (n=668)	RIBO 600 mg, 21 days on 7 days off + LETROZOLE 2.5 mg die (n=334) PLAC + LETROZOLE 2.5 mg die (n=334)	Median follow up 36.4 months ● median PFS 25.3 month vs 16 months HR:0.56 (95% CI: 0.457–0.704) ● ORR 42.5% vs 28.7% ● Median follow up 80 months ● OS (months) 63.9 vs 51.4 months ● (HR 0.76; 95% CI: 0.63–0.93)	Age: < 65y ≥65 years ● 0.51(0.39–0.68) vs 0.65(0.46–0.92) Liver or Lung mts: NO vs Yes ● 0.59 (0.42–0.83) vs 0.56(0.42–0.74) Bone only disease: NO vs Yes ● 0.55(0.43–0.70) vs 0.64(0.39–1.04) De novo disease: No vs Yes ● 0.57(0.44–0.74) vs 0.56(0.38–0.84) Prior ET: AI vs TAM vs None ● 0.37(0.23–0.59) vs 0.61(0.42–0.89) vs 0.65(0.46–0.90) Prior CT: No vs Yes 0.64(0.47–0.87) vs 0.50(0.36–0.68)	Age: < 65y ≥65 years ● 0.69(0.53–0.90) vs 0.87(0.64–0.1.17) Liver or Lung mts: NO vs Yes ● 0.71(0.53–0.96) vs 0.81(0.62–1.05) Bone only disease: NO vs Yes ● 0.77(0.61–0.96) vs 0.78(0.50–1.21) De novo disease: No vs Yes ● 0.91(0.72–1.15) vs 0.52(0.36–0.74) Prior ET: AI vs TAM vs None ● 0.63(0.32–1.24) vs 0.86(0.64–1.15)vs 0.69(0.52–0.94) Prior CT: No vs Yes 0.78(0.59–1.03) vs 0.74(0.56–0.98)
Tripathy et al^Citation4 Yardley et al^7 Lu et al^Citation10 Harbeck et al^Citation14 MONALEESA-7	Premenopausal HR+/ HER2−, advanced BC (n=672)	● RIBO 600 mg, 21 days on, 7 days off + NSAI (n = 248) ● PLAC + NSAI (n = 247) ● RIBO 600 mg, 21 days on, 7 days off + TAM 20mg/die (n = 87) ● PLAC + TAM 20 mg/die (n = 90) ● All groups: Goserelin (3.6 mg subcutaneous q28)	Median follow up 19.2 months ● median PFS (months): ● -NSAI +RIBO/PLAC: 23.8 vs 13.0 (HR:0.55, 95% CI 0.44–0.69) ● -TAM+RIB/PLAC:22.1 vs 11.0 (HR: 0.59, 95% CI.39–0.88) ● ORR 41% RIBO group vs 30% placebo group ● Median follow up 53.5 months Median OS (months): NSAI +RIBO/PLAC 58.7 vs 47.7 (HR 0.80; 95% CI: 0.62–1.04) - TAM+RIBO/PLAC: not estimable vs 49.3 months (HR 0.71, 95% CI:0.45–1.10)	Age: < 40y ≥40 years ● 0.44 (0,29–0,67) vs 0.59(0.45–0.78) Liver or Lung mts: NO vs Yes ● 0.64 (0.45–0.91) vs 0.50(0.38–0.68) Bone only disease: NO vs Yes ● 0.53(0.42–0.69) vs 0.70(0.41–1.19) Prior ET (Neoadj/adj): No vs Yes ● 0.52(0.38–0.70) vs 0.62(0.44–0.89) Prior CT (Neoadj/adj): No vs Yes 0.41(0.28–0.60) vs 0.68(0.48–0.96)	Age: < 40y ≥40 years ● 0.65(0.43–0.98) vs 0.81(0.61–0.1.06) Liver or Lung mts: NO vs Yes ● 0.70(0.50–0.97) vs 0.83(0.61–1.13) Bone only disease: NO vs Yes ● 0.76(0.59–0.98) vs 0.77(0.47–1.28) Disease free interval: DeNovo vs Recurrent ● 0.52(0.35–0.78) vs 0.94(0.71–1.24) Prior (Neo)adj ET: NO vs Yes ● 0.71(0.52–0.97) vs 0.91(0.65–1.28) Prior (Neo)adj CT: No vs Yes 0.59(0.41–0.86) vs 0.97(0.69–1.36)

Abbreviations: BC, breast cancer; FULV, fulvestrant; RIB, ribociclib; PLAC, placebo; NSAI, non steroidal aromatase inhibitor.

Table 2 Cyclin-Dependent Kinases (CDK)4/6 Inhibitors’ Toxicity Profiles

	Palbociclib + LET	Palbociclib + FULV	Ribociclib + LET	Ribociclib + FULV	Abemaciclib + FULV	Abemaciclib + AI
Adverse events all grades	Neutropenia (80%) Leukopenia (40%) Nausea (35%) Fatigue (35%) Arthralgia (33%) Alopecia (33%)	Neutropenia (80%) Leukopenia (50%) Infections (42%) Fatigue (40%) Nausea (32%)	Neutropenia (75%) Leukopenia (33%) Nausea (50%) Infections (50%) Fatigue (37%) Diarrhea (35%) Alopecia (33%)	Neutropenia (70%) Nausea (45%) Fatigue (32%) Diarrhea (29%) Leukopenia (28%) Vomiting (27%) Constipation (25%) Arthralgia (24%) Cough (22%) Headache (22%) Alopecia (19%) Rash (18%) Anemia (17%)	Neutropenia (46%) Diarrhea (86%) Nausea (45%) Fatigue (40%) Abdominal pain (35%)	Neutropenia (41%) Diarrhea (81%) Nausea (39%) Fatigue (40%) Infections (39%)
Adverse events grade 3–4	Neutropenia (66%) Leukopenia (25%)	Neutropenia (65%) Leukopenia (28%)	Neutropenia (59%) Leukopenia (21%)	Neutropenia (53%) Leukopenia (14%) Anemia (3%) Fatigue (2%) Back Pain (2%) Nausea (1%) Constipation (1%) Headache (1%)	Neutropenia (24%)	Neutropenia (21%)

Abbreviations: FULV, fulvestrant; LET, letrozole; AI, aromatase inhibitors.

Table 3 Neoadjuvant Studies with Ribociclib in ER+ Breast Cancer

Study/Author	Phase	Drugs	N* of Pts	Primary End Point	Results
MONALEESA-1/Curigliano et al^Citation33	III	L (Arm A) vs L+R400 mg (Arm B) vs L+R 600 mg/d (Arm C)	14	Mean decrease of Ki-67 levels	Mean decreases in Ki67-levels: arm A 69% vs Arm B 96% vs Arm C 92%
FELINE/Khan et al ASCO 2020^Citation34	II	L vs L with R at 2 doses for 24 weeks	120	Changes in PEPI score	Addition of R to L did not result in more women with a PEPI score of 0.
CORALLEEN/Prat et al^Citation36	III	L + R vs standard CT	106	Rate of RCB	RCB 0/I was achieved in 11.8% in CT arm vs 6.1% in in L+R arm

Abbreviations: L, letrozole; R, ribociclib; RCB, residual cancer burden.

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