MONALEESA-2 Interim Analysis: Ribociclib Plus Letrozole Adverse - - PowerPoint PPT Presentation

MONALEESA-2 Interim Analysis: Ribociclib Plus Letrozole

Outcome Ribociclib + Letrozole (n=334) Placebo + Letrozole (n=334) Median PFS, months (95% CI) NR (19.3, NR) 14.7 (13.0, 16.5) Hazard ratio (95% CI); P value 0.56* (0.43, 0.72); 0.00000329 PFS rate (%) at 12 months (95% CI) 72.8 (67.3, 77.6) 60.9 (55.1, 66.2) PFS rate (%) at 18 months (95% CI) 63.0 (54.6, 70.3) 42.2 (34.8, 49.5)

*This represents a 44% lower relative risk of progression. NR=not reached. Hortobagyi G et al. N Engl J Med. 2016; Oct 7 [Epub ahead of print].

Interim Analysis of Primary Endpoint Adverse Events in ≥30% of Patients in Either Group

Adverse event, any grade (%) Ribociclib + Letrozole (n=334) Placebo + Letrozole (n=330) Neutropenia 74.3 5.2 Nausea 51.5 28.5 Infections 50.3 42.4 Fatigue 36.5 30.0 Diarrhea 35.0 22.1 Alopecia 33.2 15.5 Leukopenia 32.8 3.9

Neoadjuvant Studies of CDK4/6 Inhibitors in Combination with ET

Abemaciclib* (Abem) (N=173)1 Palbociclib (Palbo) (N=50)2 Ribociclib (Ribo) (N=14)3 ET Anastrozole (ANZ) ANZ Letrozole (LET) Study design Phase 2; randomized for first 2 weeks (abem, n=58; ANZ, n=59; combo, n=56), then

• pen label combo for 14 weeks

Phase 2; single arm 28-day cycle 0: ANZ alone 28-day cycles 1-4 ANZ + palbo Phase 2; randomized; Arm 1: LET 2.5 mg (n=4) Arm 2: LET + ribo 400 mg (n=6) Arm 3: LET + ribo 600 mg (n=4) Primary endpoint Ki67 change from baseline to week 2 (geometric mean) % with complete cell cycle arrest (CCCA; Ki67 ≤2.7%) after 15 days of ANZ + palbo Ki67 change from baseline to day 14 (±3 days) Result Abem + ANZ: –93.5%; n=23† Abem: –93.1%; n=19† ANZ: –71.0%; n=22 87% (n=45); 90% CI: 75% to 94% Arm 1: –69% (range 38%–100%; n=2) Arm 2: –96% (range 78%–100%; n=6) Arm 3: –92% (range 75%–100%; n=3) Additional findings Pts with Ki67 <2.7: Abem + ANZ: 69.6% Abem: 68.4% ANZ: 22.7% ANZ alone (n=43): 26% Levels of phosphorylated Rb decreased in 5 of 8 evaluable patients in Arms 2 and 3 (mean 59% decrease)

*150 mg bid; †One-sided P<0.001 vs ANZ

• 1. Hurvitz S et al. Presented at the European Society of Medical Oncology Annual Congress; October 7–11, 2016; Copenhagen, Denmark:

LBA13; 2. Ma C et al. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res. 2016;76(4 Suppl):Abstract S6-05; 3. Curigliano G et al. Breast. 2016;28:191-198.

Common AEs in Neoadjuvant Studies of CDK4/6 Inhibitor + ET

Drug Combination Key Findings Abemaciclib + anastrozole1 3 most common investigator-assessed treatment-emergent AEs (any grade) in all groups combined (N=173) Diarrhea* (46%) Constipation (36%) Nausea (34%) 3 most common laboratory abnormalities (any grade) in all groups combined (N=173) Creatinine increased (93%) Neutrophil count decreased (65%) WBC decreased (61%) Palbociclib + anastrozole2 3 most common AEs (any grade) with combination therapy (n=50) Neutropenia (56%) Leukopenia (46%) Fatigue (40%) Ribociclib + letrozole3 Most common treatment-related AEs (n > 1; any grade) with combination therapy (arms 2 and 3 combined; n=10) Nausea (20%) Asthenia (20%) QTcF prolongation (20%) Decreased appetite (20%)

• 1. Hurvitz S et al. Presented at the European Society of Medical Oncology Annual Congress; October 7–11,

2016; Copenhagen, Denmark: LBA13; 2. Ma C et al. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res. 2016;76(4 Suppl):Abstract S6-05; 3. Curigliano G et al. Breast. 2016;28:191-198.

*Loperamide was administered as primary prophylaxis with each abemaciclib dose