1. MONARCH 2: Phase III Study of Abemaciclib + Fulvestrant in HR+/HER2- Advanced Breast Cancer After Progression on Endocrine Therapy
CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois
*Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals
HR, hormone receptor.
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. MONARCH 2: CDK4/6 Inhibition in HR+ Breast Cancer
Estrogen stimulates cyclin D1 expression, which activates CDK4 and CDK6 and leads to cell-cycle progression[1] 
Abemaciclib: selective CDK4/6 inhibitor
Continuous administration leads to sustained cell-cycle arrest, which can promote cell apoptosis or senescence[ 2]
Breakthrough Therapy designation in refractory metastatic breast cancer based on single-agent activity in phase I trial
Current phase III trial evaluated abemaciclib + fulvestrant in pts with HR+/HER2- advanced breast cancer who progressed on endocrine therapy[3]
HR, hormone receptor.
1. Altucci L, et al. Oncogene. 1996;12: Torres-Guzmán R, et al. Oncotarget. 2017;[Epub ahead of print]. 3. Sledge GW, et al. ASCO Abstract 1000.
Slide credit: clinicaloptions.com

3. MONARCH 2: Study Design Abemaciclib 150 mg BID* +
Stratified by metastatic site, ET resistance (primary vs secondary)
Abemaciclib 150 mg  BID* +
Fulvestrant 500 mg on Days 1, 15, 29 and once monthly thereafter 
(n = 446)
Patients with HR+/HER2- advanced breast cancer who progressed on 1 line of ET (neoadjuvant, adjuvant, or first line); pre/peri/post menopausal; no prior chemo for metastatic disease; ECOG PS 0/1
(N = 669)
Median follow-up: mos
Placebo +
Fulvestrant 500 mg  on Days 1, 15, 29 and once monthly thereafter 
(n = 223)
ECOG, Eastern Cooperative Oncology Group; ET, endocrine therapy; HR, hormone receptor; PS, performance status.
*Dose reduced from 200 mg to 150 mg after 178 pts enrolled.
Pts enrolled at 142 centers in 19 countries
Primary endpoint: PFS (investigator assessed)
Secondary endpoints: OS, ORR, clinical benefit rate, safety
Slide credit: clinicaloptions.com
Sledge GW, et al. ASCO Abstract 1000.

4. MONARCH 2: Baseline Characteristics
Abemaciclib + Fulvestrant (n = 446)
Placebo + Fulvestrant (n = 223)
Median age, yrs (range)
59 (32-91)
62 (32-87)
Primary ET resistance, % 25 26
Most recent ET, %
Neoadjuvant/adjuvant
Metastatic 59 38 60
Prior aromatase inhibitor, % 71 67
PgR positive, % 76 77
Metastatic site, %
Visceral
Bone only
Other (nonvisceral soft tissue) 55 28 17 57
Measureable disease, % 74
Postmenopausal, % 83 81
ET, endocrine therapy
Slide credit: clinicaloptions.com
Sledge GW, et al. ASCO Abstract 1000.

5. MONARCH 2: PFS 20 40 60 80
100 3 6 9 12 15 18 21 24 27 30
PFS (%)
Mos
446
223
Patients at risk:
Abemaciclib
Placebo
367
165
314
123
281
103
234
171 61
101 32 65 13 4 2 1
Median PFS, Mos
Abemaciclib + fulvestrant: 16.4
Placebo + fulvestrant: 9.3
HR: 0.55 (95% CI: ; P < )
PFS benefit with addition of abemaciclib to fulvestrant observed across all pt subgroups, except those with nonvisceral soft tissue metastases
ORR, abemaciclib cohort vs placebo cohort: 35.2% vs 16.1%
Sledge GW, et al. ASCO Abstract Reproduced with permission.

6. MONARCH 2: Drug Exposure and Overall Safety
Characteristic
Abemaciclib + Fulvestrant (n = 441)
Placebo + Fulvestrant (n = 223)
Median dose intensity, mg/day
273
298
Median number of cycles 15 9
Dose modification of due to AEs, %
Discontinuation
Reduction
15.9
42.9
3.1
1.3
Serious AEs, %
22.4
10.8
Deaths due to AEs, %
Related to treatment
2.0
0.7*
0.9
*n = 3: sepsis in 2 pts in whom guidance regarding G-CSF administration and dose reduction not followed; viral pneumonia in 1 pt receiving steroids for spinal stenosis.
AE, adverse event; G-CSF, granulocyte colony-stimulating factor
Discontinuation of either drug due to AE
24% preamendment
13% postamendment
Slide credit: clinicaloptions.com
Sledge GW, et al. ASCO Abstract 1000.

7. MONARCH 2: Treatment-Emergent AEs
Treatment- Emergent AE Occurring in ≥ 20% in Either Arm, %
Abemaciclib + Fulvestrant (n = 441)
Placebo + Fulvestrant (n = 223)
All Grades
Grade 3/4
Any
98.6
60.5
89.2
22.8
Diarrhea*
86.4
13.4
24.7
0.4
Neutropenia
46.0
26.5
4.0
1.7
Nausea
45.1
2.7
22.9
0.9
Fatigue
39.9
26.9
Abdominal pain
35.4
2.5
15.7
Anemia
29.0
7.2
3.6
Leukopenia
28.3
8.8
1.8
Decreased appetite
1.1
12.1
Vomiting
25.9
10.3
Headache
20.2
0.7
15.2
AE, adverse event.
*Incidence of diarrhea greatly reduced after starting abemaciclib dose amended from 200 mg to 150 mg.
Slide credit: clinicaloptions.com
Sledge GW, et al. ASCO Abstract 1000.

8. MONARCH 2: Investigator Conclusions
Adding abemaciclib to fulvestrant effective in HR+/HER2- advanced breast cancer that progressed on prior ET
Significant improvement in PFS: 16.4 vs 9.3 mos (HR: 0.553; P < )
Abemaciclib generally well tolerated
Grade 3/4 neutropenia: 26.5%
Diarrhea typically occurred early, managed with dose adjustment and antidiarrheal medication
monarchE trial of adjuvant abemaciclib + ET in HR+/HER2- high-risk breast cancer will begin recruitment Q3 2017
ET, endocrine therapy; HR, hormone receptor.
Slide credit: clinicaloptions.com
Sledge GW, et al. ASCO Abstract 1000.

9. Go Online for More CCO Coverage of ASCO 2017!
Short slideset summaries and additional CME-certified analyses with expert faculty commentary on key studies in:
Breast, gastrointestinal, genitourinary, lung, and skin cancers
Gynecologic and hematologic malignancies
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