1. Abemaciclib + Endocrine or HER2-Targeted Therapies in Metastatic Breast Cancer
CCO Independent Conference Coverage*: The 2015 Annual Meeting of the CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2015
San Antonio, Texas
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This program is supported by educational grants from Genentech and Novartis.

2. Abemaciclib Combinations in MBC: Background
Abemaciclib: investigational oral small molecule inhibitor of CDK 4/6[1]
Induces cell cycle arrest in Rb-proficient cancers
Exhibits clinical activity as single agent[2] and acceptable safety profiles in combination with either fulvestrant[3] or aromatase inhibitors[4] in previously treated HR+ MBC
Current study evaluated safety and antitumor activity of abemaciclib when given with endocrine or HER2-targeted therapies for the treatment of MBC[5]
HR, hormone receptor; MBC, metastatic breast cancer.
1. Gelbert LM, et al. Invest New Drugs. 2014;32: Tolaney SM, et al. SABCS Abstract P Patnaik A, et al. ASCO Abstract Tolaney SM, et al. ASCO Abstract Goetz MP, et al. SABCS Abstract P
Slide credit: clinicaloptions.com

3. Abemaciclib Combinations in MBC: Study Design
Phase Ib study
Primary objective: safety
Secondary objective: antitumor activity, PK
Abemaciclib 200 mg Q12H +
Cohort A: Letrozole 2.5 mg QD (n= 20)
Cohort B: Anastrozole 1 mg QD (n = 16)
Cohort C: Tamoxifen 20 mg QD (n = 15)
Cohort D: Exemestane 25 mg QD (n = 15)
Cohort E*: Abemaciclib 150/200 mg Q12H +
Exemestane 25 mg QD + Everolimus 5 mg QD (n = 17)
Pts with HR+, HER2- MBC;
premenopausal + ovarian suppression or postmenopausal;
ECOG PS 0 or 1;
no prior CT for MBC
(N = 83)
Pts with HER2+ MBC;
pre- or postmenopausal; ECOG PS 0 or 1;
≥ 1 prior CT for MBC
(N = 10)
Cohort F:* Abemaciclib 150/200 mg Q12H +
+ Trastuzumab 6-8 mg/kg IV on Day 1 of 21-day cycle (n = 10)
CT, chemotherapy; ECOG, Eastern Cooperative Oncology Group; HR, hormone receptor; MBC, metastatic breast cancer; PK, pharmacokinetics; PS, performance status.
*Abemaciclib dose escalation with fixed doses of the combination drug(s).
Sequential enrollment. Sequential dose adjustments of 50 mg allowed for toxicity.
Abemaciclib given until progression, unacceptable toxicity, or pt elected to stop.
Goetz MP, et al. SABCS Abstract P ClinicalTrials.gov. NCT
Slide credit: clinicaloptions.com

4. Abemaciclib Combinations in MBC: Baseline Characteristics
Abe + Let
(n = 20)
Abe + Ana
(n = 16)
Abe + Tam
Abe + Exe
(n = 15)
Abe + Exe/Eve
Abe + Tras
150 mg
(n = 13)
200 mg
(n = 4)
(n = 6)
Age, median yrs (range)
59.0
(33-73)
55.5
(26-72)
59.5
(46-77)
52.0
(40-73)
57.0
(41-73)
64.5
(50-68)
53.5
(45-64)
(48-76)
White race, %
100 88 93 92 75
ECOG PS, % 1 2 80 15 5 81 19 25 20 31 61 8 67 33
Prior systemic therapies, median n (range)
(1-4) 3
(1-8)
(1-6) 4
2.5
(2-5)
10.5
(1-15)
6.5
(4-8)
Measurable disease, % 45 56 50 62 83
HR/HER status, %
HR+/HER-
HR+/HER+
HR-/HER2+ 17
Abe, abemaciclib; Ana, anastrozole; ECOG, Eastern Cooperative Oncology Group; Eve, everolimus; Exe, exemestane; HR, hormone receptor; Let, letrozole; MBC, metastatic breast cancer; PS, performance status; Tam, tamoxifen; Tras, trastuzumab.
Slide credit: clinicaloptions.com
Goetz MP, et al. SABCS Abstract P

5. Abemaciclib Combinations in MBC: Treatment-Emergent AEs, Cohorts A-D
TEAEs in > 33% of Pts
in Any Cohort, %
Abe + Let (n = 20)
Abe + Ana (n = 16)
Abe + Tam (n = 16)
Abe + Exe (n = 15)
Grade 1/2
Grade 3
Diarrhea 55 45 60 31 63 67 27
Fatigue 65 20 19 44 53 13
Nausea 15 75 6
Vomiting 30 10 40
Anemia 25
Decreased appetite 5 50
Abdominal pain
Dehydration 7
Rash
WBC decreased 70 56
Neutrophils decreased
Lymphocytes decreased
Platelet count decreased
Creatinine increased
100 88
Hypercalcemia
Abe, abemaciclib; AE, adverse event; Ana, anastrozole; Exe, exemestane; Let, letrozole; MBC, metastatic breast cancer; TEAE, treatment-emergent adverse event; Tam, tamoxifen; WBC, white blood cell.
Slide credit: clinicaloptions.com
Goetz MP, et al. SABCS Abstract P

6. Abemaciclib Combinations in MBC: Treatment-Emergent AEs, Cohorts E and F
TEAEs in > 33% of Pts in Any Cohort, %
Abe + Exe/Eve
Abe + Tras
150 mg (n = 13)
200 mg (n = 4)
150 mg (n = 4)
200 mg (n = 6)
Grade 1/2
Grade 3
Diarrhea 62 15 75 25 50 17 83
Fatigue 54 8
100 33
Nausea 31
Vomiting
Anemia 23
Decreased appetite 38
Abdominal pain 46
Dehydration
Rash
WBC decreased
Neutrophils decreased
Lymphocytes decreased
Platelet count decreased
Creatinine increased 92
Abe, abemaciclib; AE, adverse event; Eve, everolimus; Exe, exemestane; G, grade; MBC, metastatic breast cancer; TEAE, treatment-emergent adverse event; Tras, trastuzumab; WBC, white blood cell.
Slide credit: clinicaloptions.com
Goetz MP, et al. SABCS Abstract P

7. Abemaciclib Combinations in MBC: PFS and Tumor Response, Cohorts A-E
Abe + Let
(n = 20)
Abe + Ana
(n = 16)
Abe + Tam
Abe + Exe
(n = 15)
Abe + Exe/Eve
150 mg
(n = 13)
200 mg
(n = 4)
Best overall response CR PR SD PD
Unknown 10 50 30 19 69 6 56 7 27 40 20 15 39 46 75 25
ORR (CR + PR)
All pts
Pts with measurable disease 22 33 38
Disease control rate
(CR + PR + SD) 60 88 73 54
Clinical benefit rate
(CR + PR + SD > 24 wks) 81
Not mature
6-mo PFS, % (95% CI)
76.2
( )
66.7
( )
73.3
( )
75.2
( )
12-mo PFS, % (95% CI)
79.4
( )
64.2
( )
Abe, abemaciclib; Ana, anastrozole; Eve, everolimus; Exe, exemestane; Let, letrozole; MBC, metastatic breast cancer; PD, progressive disease; SD, stable disease; Tam, tamoxifen; Tras, trastuzumab.
Slide credit: clinicaloptions.com
Goetz MP, et al. SABCS Abstract P

8. Abemaciclib Combinations in MBC: Conclusions
Abemaciclib + endocrine and HER2-targeted therapies achieved tumor responses in pts with MBC
No observed drug–drug interactions between abemaciclib and tamoxifen, exemestane, or trastuzumab
Most frequent grade 3 toxicities included diarrhea, neutropenia, and leukopenia
Ongoing randomized phase III trials are evaluating abemaciclib + AIs and the antiestrogen fulvestrant in MBC
Recommended abemaciclib dose 150 mg Q12H in combination with AI, tamoxifen, or exemestane
AI, aromatase inhibitor; MBC, metastatic breast cancer.
Goetz MP, et al. SABCS Abstract P ClincalTrials.gov. NCT ClincalTrials.gov. NCT
Slide credit: clinicaloptions.com

9. Go Online for More CCO Coverage of SABCS 2015!
Short slideset summaries of all the key data Additional CME-certified analysis with expert faculty commentary on all the key studies
clinicaloptions.com/oncology