Only CDK4 & 6 inhibitor approved across HR+, HER2− MBC in combination and as a single agent1

At the time of PFS analysis, overall survival data were not mature. 20% and 19% of patients had died in MONARCH 2 and MONARCH 3, respectively.1

*The percentage of events at the time of analysis was 49.8% (n=222) and 70.4% (n=157) in the Verzenio + fulvestrant and placebo + fulvestrant arms, respectively.1

The percentage of events at the time of analysis was 42.1% (n=138) and 65.5% (n=108) in the Verzenio + an AI and placebo + an AI arms, respectively.1

In patients with measurable disease. ORR was defined as the proportion of patients with CR + PR, and does not include stable disease. PR defined as ≥30% target lesion size per RECIST 1.1.2-5

AI=aromatase inhibitor; CDK4 & 6=cyclin-dependent kinases 4 and 6; CI=confidence interval; CR=complete response; HER2−=human epidermal growth factor receptor 2 negative; HR=hazard ratio; HR+=hormone receptor positive; MBC=metastatic breast cancer; NR=not reached; ORR=objective response rate; PFS=progression-free survival; PR=partial response; RECIST 1.1=Response Evaluation Criteria in Solid Tumors version 1.1.

Select Important Safety Information

The labeling for Verzenio contains warnings and precautions for diarrhea, neutropenia, hepatotoxicity, venous thromboembolism, and embryofetal toxicity. Instruct patients at the first sign of loose stools to initiate antidiarrheal therapy, increase oral fluids, and notify their healthcare provider. Perform CBC and LFTs prior to the start of Verzenio treatment, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Based on results, Verzenio may require dose modification. Monitor patients for signs and symptoms of thrombosis and pulmonary embolism and treat as medically appropriate. Advise patients of potential risk to a fetus and to use effective contraception. See full Prescribing Information for further management instructions.

Most common adverse reactions in the MONARCH 1, 2, and 3 trials (all grades, ≥20%) were diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, alopecia, and thrombocytopenia.

Please see full Prescribing Information for additional information.

For women with HR+, HER2− MBC, including those with concerning clinical characteristics3,6-9*

*Disease characteristics that typically confer a less favorable prognosis. Primary resistance and visceral disease were concerning clinical characteristics in MONARCH 2.

Patient: PamPatient: Pam

Hypothetical patient profile.

Primary resistance is defined as relapse while on the first 2 years of adjuvant ET, or progressive disease within the first 6 months of first-line endocrine therapy for metastatic breast cancer.1

ET=endocrine therapy.

In HR+, HER2− MBC

MONARCH 2: Verzenio + fulvestrant in patients who recurred or progressed on endocrine therapy (ET)1

Concerning clinical characteristics at baseline1,3,6-9*:

  • 56% of patients had visceral disease1
  • 25% of patients had primary endocrine therapy resistance1
    • Primary resistance is defined as relapse while on the first 2 years of adjuvant ET, or progressive disease within the first 6 months of first-line endocrine therapy for metastatic breast cancer1

*Disease characteristics that typically confer a less favorable prognosis. Primary resistance and visceral disease were concerning clinical characteristics in MONARCH 2.

MONARCH 2: A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL1,3
MONARCH 2 Trial DesignMONARCH 2 Trial Design

No women enrolled in the trial received prior treatment with CDK4 & 6 inhibitors.1

Pre/perimenopausal women were enrolled in the study and received the gonadotropin-releasing hormone agonist goserelin for at least 4 weeks prior to and for the duration of MONARCH 2.1

§17% of patients were pre/perimenopausal.1

Before a study amendment changed the starting dose to 150 mg, 121 of the 446 ITT patients (27%) initially received a 200-mg starting dose. Median duration for 200-mg dosing was 34 days.3

Each cycle was 28 days.3

BID=twice a day; IM=intramuscular; ITT=intent-to-treat; PO=orally.

For women with HR+, HER2− MBC

>16-month median PFS in women who recurred or progressed on ET1

MEDIAN PFS1,3
PFS in MONARCH 2PFS in MONARCH 2
  • The percentage of events at the time of analysis was 49.8% (n=222) and 70.4% (n=157) in the Verzenio + fulvestrant and placebo + fulvestrant arms, respectively1
  • At the time of the primary analysis of PFS, overall survival data were not mature (20% of patients had died)1

In HR+, HER2− MBC with recurrence or progression on ET

PFS results in women with concerning clinical characteristics were consistent with the ITT population1,3,6-9*

*Disease characteristics that typically confer a less favorable prognosis. Primary resistance and visceral disease were concerning clinical characteristics in MONARCH 2.

MEDIAN PFS IN PRIMARY RESISTANCE12
Median PFS in primary resistance in MONARCH 2Median PFS in primary resistance in MONARCH 2
  • Primary resistance is defined as relapse while on the first 2 years of adjuvant endocrine therapy, or progressive disease within the first 6 months of first-line endocrine therapy for MBC1
  • Preplanned subgroup analyses of PFS were performed for stratification factors of disease site, including visceral disease, and endocrine resistance, including primary resistance. The analyses were not adjusted for multiplicity and the study was not powered to test the effect of Verzenio + fulvestrant among subgroups12
MEDIAN PFS IN VISCERAL DISEASE12
Median PFS in visceral disease in MONARCH 2]Median PFS in visceral disease in MONARCH 2]
  • Visceral disease was defined as at least 1 lesion on an internal organ or in the third space and could have included lung, liver, pleural, or peritoneal metastatic involvement13
  • Preplanned subgroup analyses of PFS were performed for stratification factors of disease site, including visceral disease, and endocrine resistance, including primary resistance. The analyses were not adjusted for multiplicity and the study was not powered to test the effect of Verzenio + fulvestrant among subgroups12

ITT=intent-to-treat.

In HR+, HER2− MBC

Nearly 50% ORR in women who recurred or progressed on ET1

ORR IN PATIENTS WITH MEASURABLE DISEASE1,3
MONARCH 2 ORR: 48.1%MONARCH 2 ORR: 48.1%]
MEDIAN DURATION OF RESPONSE (mDOR)14*
MONARCH 2 mDoR: 22.8 monthsMONARCH 2 mDoR: 22.8 months
  • At the time of the primary analysis of PFS, overall survival data were not mature (20% of patients had died).1 Post hoc analysis of ITT population based on 158 and 37 women in the Verzenio + fulvestrant and placebo + fulvestrant arms, respectively, who had a best response of partial response (PR) or complete response (CR)14
  • ORR was defined as the proportion of patients with CR + PR, and does not include stable disease1,5*
  • DoR was a secondary endpoint of the trial.3 There was no prespecified statistical procedure controlling for type I error

More than doubled ORR vs fulvestrant alone1

*PR defined as ≥30% reduction in target lesion size per RECIST 1.1.3,5

ITT=intent-to-treat; ORR=objective response rate.

For women with HR+, HER2− MBC, including those with concerning clinical characteristics4,10,11,15-18*

*Disease characteristics that typically confer a less favorable prognosis. Liver metastases and treatment-free interval <36 months were concerning clinical characteristics in MONARCH 3. Exploratory subgroup analyses of PFS were performed for patients with these characteristics.

Patient: AnnaPatient: Anna

Hypothetical patient profile.

In HR+, HER2− MBC

MONARCH 3: Verzenio + an AI in patients receiving initial endocrine-based therapy1,4

Patient population at baseline, including those with concerning clinical characteristics1,4,15-18*

  • 47% of patients received prior (neo)adjuvant endocrine therapy, including 15% who had a treatment-free interval <36 months4
  • 39% of patients had received chemotherapy1
  • 53% of patients had visceral disease, including 16% with liver metastases1,4
  • 22% of patients had bone-only disease1

*Disease characteristics that typically confer a less favorable prognosis. Liver metastases and treatment-free interval <36 months were concerning clinical characteristics in MONARCH 3. Exploratory subgroup analyses of PFS were performed for patients with these characteristics.10,11

MONARCH 3: A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL1,4
MONARCH 3 Trial DesignMONARCH 3 Trial Design

Each cycle was 28 days.4

80% of patients received letrozole and 20% received anastrozole.1

AI=aromatase inhibitor; BID=twice a day; ECOG PS=Eastern Cooperative Oncology Group Performance Status; PO=orally; QD=once a day.

For postmenopausal women with HR+, HER2− MBC

>28-month median PFS as initial endocrine-based therapy1

MEDIAN PFS1
MONARCH 3 median PFS 28.2 monthsMONARCH 3 median PFS 28.2 months
  • The percentage of events at the time of analysis was 42.1% (n=138) and 65.5% (n=108) in the Verzenio + an AI and placebo + an AI arms, respectively1
  • At the time of the PFS analysis, 19% of patients had died, and overall survival data were immature1

PFS results in women with concerning clinical characteristics1,4,10,15*

*Disease characteristics that typically confer a less favorable prognosis. Liver metastases and treatment-free interval <36 months were concerning clinical characteristics in MONARCH 3.4,10,11,15-18

Exploratory Subgroup Analysis

MEDIAN PFS IN WOMEN WITH LIVER METASTASES (N=78)10
MONARCH 3 15.0 months median PFS in women with liver metastasesMONARCH 3 15.0 months median PFS in women with liver metastases
  • Exploratory subgroup analysis of PFS was performed for the subgroups of patients with and without liver metastases. Estimated hazard ratios and CIs for the within subgroup analyses that were adjusted for treatment interaction are shown. The analyses were not adjusted for multiplicity and the study was not powered to test the effect of Verzenio + an AI among subgroups10

Exploratory Subgroup Analysis

MEDIAN PFS IN WOMEN WITH TREATMENT-FREE INTERVAL <36 MONTHS (N=76)11
29.5 months median PFS in MONARCH 329.5 months median PFS in MONARCH 3
  • Exploratory subgroup analysis of PFS was performed for the subgroups of patients who had a treatment-free interval <36 months after completion of adjuvant endocrine therapy. Estimated hazard ratios and CIs for the within subgroup analyses that were adjusted for treatment interaction are shown. In addition, the Kaplan-Meier plot of PFS by investigator assessment was provided. The analyses were not adjusted for multiplicity and the study was not powered to test the effect of Verzenio + AI among subgroups11

For postmenopausal women with HR+, HER2− MBC

55% ORR as initial endocrine-based therapy1

ORR IN PATIENTS WITH MEASURABLE DISEASE1,19*
MONARCH 3 55.4% ORRMONARCH 3 55.4% ORR
MEDIAN DURATION OF RESPONSE (mDoR)20
MONARCH 3 median duration of response 27.4 monthsMONARCH 3 median duration of response 27.4 months
  • At the time of the PFS analysis, 19% of patients had died, and overall survival data were immature1
  • ORR was defined as the proportion of patients with CR + PR and does not include stable disease1
  • DoR was a secondary endpoint of the trial.4 There was no prespecified statistical procedure controlling for type I error
  • Analysis based on the ITT population of women (Verzenio + an AI, N=163; placebo + an AI, N=61) who had a best response of PR or CR20

*Based upon confirmed responses.1

For women with HR+, HER2− MBC, including those with concerning clinical characteristics2,6-8*

*Disease characteristics that typically confer a less favorable prognosis. Visceral disease and progression on ET and prior chemotherapy in the metastatic setting were concerning clinical characteristics in MONARCH 1.

Patient: CarlaPatient: Carla

Hypothetical patient profile.

For heavily pretreated patients with HR+, HER2− MBC

MONARCH 1: The first and only CDK4 & 6 inhibitor approved as a single agent1

Based on results from MONARCH 1, a phase II, single-arm trial in heavily pretreated women with high disease burden, including those with concerning clinical characteristics1,2,6-8*

  • 100% of women received ET and 1 to 2 chemotherapy regimens in the metastatic setting (N=132)1*
  • 90% of women had visceral disease; 71% had liver metastases1,2*
  • 51% of women had 3 or more metastatic sites1

*Disease characteristics that typically confer a less favorable prognosis. Visceral disease and progression on ET and prior chemotherapy in the metastatic setting were concerning clinical characteristics in MONARCH 1.2,6-8

A SEPARATE, PHASE II, SINGLE-ARM TRIAL
MONARCH 1 Trial DesignMONARCH 1 Trial Design

In a study protocol deviation, 1 patient received 3 chemotherapy regimens in the metastatic setting, first receiving capecitabine, followed by 2 regimens of docetaxel separated by a treatment-free interval of >1 year.21

Per RECIST 1.1, target lesion(s) are defined by 1 to 5 measurable lesions (a maximum of 2 lesions per organ) present at baseline that are representative of all involved organs.5

§ORR was defined as the proportion of patients with CR + PR, with PR defined as ≥30% reduction in target lesion size per RECIST 1.1. ORR does not include patients with stable disease.2,5

For heavily pretreated patients with HR+, HER2− MBC

MONARCH 1 ORR 19.7%
OBJECTIVE RESPONSE RATE1
MONARCH 1 ORR 19.7%
MEDIAN DURATION OF RESPONSE (mDoR)1
MONARCH 1 mDoR: 8.6 months
MONARCH 1 mDoR: 8.6 months

*PR defined as ≥30% reduction in target lesion size per RECIST 1.1.2,5

Per investigator assessment.2,22

Among 26 patients (investigator assessed) and 23 patients (independent review) who had a partial response.1

National Comprehensive Cancer Network® (NCCN®) Recommendations

NCCN recommends abemaciclib (Verzenio™) both in combination with fulvestrant or an AI and as a single agent23

NCCN recommendations Category 1* Abemaciclib (Verzenio) + fulvestrant and  Abemaciclib (Verzenio) + an aromatase inhibitor. Category 2A Abemaciclib (Verzenio) as a single agentNCCN recommendations Category 1* Abemaciclib (Verzenio) + fulvestrant and  Abemaciclib (Verzenio) + an aromatase inhibitor. Category 2A Abemaciclib (Verzenio) as a single agent

*Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.23

Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.23

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

References: 1. Verzenio [package insert]. Indianapolis, IN: Eli Lilly and Company; 2018. 2. Dickler MN, Tolaney SM, Rugo HS, et al. MONARCH 1, a phase 2 study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2- metastatic breast cancer. Clin Cancer Res. 2017;23;5218-5224. 3. Sledge GW Jr, Toi M, Neven P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2− advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017;35:2875-2884. 4. Goetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35:3638-3646. 5. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228-247. 6. Imkampe A, Bendall S, Bates T. The significance of the site of recurrence to subsequent breast cancer survival. Eur J Surg Oncol. 2007;33:420-423. 7. Largillier R, Ferrero JM, Doyen J, et al. Prognostic factors in 1038 women with metastatic breast cancer. Ann Oncol. 2008;19:2012-2019. 8. Solomayer EF, Diel IJ, Meyberg GC, Gollan C, Bastert G. Metastatic breast cancer: clinical course, prognosis and therapy related to the first site of metastasis. Breast Cancer Res Treat. 2000;59:271-278. 9. Cardoso F, Costa A, Senkus E, et al. 3rd ESO–ESMO international consensus guidelines for advanced breast cancer (ABC 3). Breast. 2017;31:244-259. 10. Data on file. Lilly USA, LLC. ONC20180108a. 11. Data on file. Lilly USA, LLC. ONC20180328a. 12. Data on file. Lilly USA, LLC. ONC20180103a. 13. Data on file. Lilly USA, LLC. ONC20171128a. 14. Data on file. Lilly USA, LLC. ONC20180126a. 15. Gerratana L, Fanotto V, Bonotto M, et al. Pattern of metastasis and outcome in patients with breast cancer. Clin Exp Metastasis. 2015;32:125-133. 16. Vogel CL, Azevedo S, Hilsenbeck S, East DR, Ayub J. Survival after first recurrence of breast cancer: the Miami experience. Cancer. 1992;70:129-135. 17. Chang J, Clark GM, Allred DC, Mohsin S, Chamness G, Elledge RM. Survival of patients with metastatic breast carcinoma: importance of prognostic markers of the primary tumor. Cancer. 2003;97:545-553. 18. Yamamoto N, Watanabe T, Katsumata N, et al. Construction and validation of a practical prognostic index for patients with metastatic breast cancer. J Clin Oncol. 1998;16:2401-2408. 19. Data on file. Lilly USA, LLC. ONC20180214a. 20. Data on file. Lilly USA, LLC. ONC20180122a. 21. Data on file. Lilly USA, LLC. ONC20170111b. 22. Data on file. Lilly USA, LLC. ONC20171201a. 23. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.1.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed March 22, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org.

Indication

Verzenio is indicated for the treatment of hormone receptor–positive (HR+), human epidermal growth factor receptor 2−negative (HER2−) advanced or metastatic breast cancer (MBC):

  • In combination with fulvestrant for women with disease progression following endocrine therapy
  • In combination with an aromatase inhibitor (AI) for postmenopausal women as initial endocrine-based therapy
  • As a single agent for adult patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting

Important Safety Information

Diarrhea occurred in 81% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 86% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and 90% of patients receiving Verzenio alone in MONARCH 1. Grade 3 diarrhea occurred in 9% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 13% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and in 20% of patients receiving Verzenio alone in MONARCH 1. Episodes of diarrhea have been associated with dehydration and infection.

Diarrhea incidence was greatest during the first month of Verzenio dosing. In MONARCH 3, the median time to onset of the first diarrhea event was 8 days, and the median duration of diarrhea for Grades 2 and 3 were 11 and 8 days, respectively. In MONARCH 2, the median time to onset of the first diarrhea event was 6 days, and the median duration of diarrhea for Grades 2 and 3 were 9 days and 6 days, respectively. In MONARCH 3, 19% of patients with diarrhea required a dose omission and 13% required a dose reduction. In MONARCH 2, 22% of patients with diarrhea required a dose omission and 22% required a dose reduction. The time to onset and resolution for diarrhea were similar across MONARCH 3, MONARCH 2, and MONARCH 1.

Instruct patients that at the first sign of loose stools, they should start antidiarrheal therapy such as loperamide, increase oral fluids, and notify their healthcare provider for further instructions and appropriate follow-up. For Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization, discontinue Verzenio until toxicity resolves to ≤Grade 1, and then resume Verzenio at the next lower dose.

Neutropenia occurred in 41% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 46% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and 37% of patients receiving Verzenio alone in MONARCH 1. A Grade ≥3 decrease in neutrophil count (based on laboratory findings) occurred in 22% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 32% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and in 27% of patients receiving Verzenio alone in MONARCH 1. In MONARCH 3, the median time to first episode of Grade ≥3 neutropenia was 33 days, and in MONARCH 2 and MONARCH 1, was 29 days. In MONARCH 3, median duration of Grade ≥3 neutropenia was 11 days, and for MONARCH 2 and MONARCH 1 was 15 days.

Monitor complete blood counts prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Febrile neutropenia has been reported in <1% of patients exposed to Verzenio in the MONARCH studies. Two deaths due to neutropenic sepsis were observed in MONARCH 2. Inform patients to promptly report any episodes of fever to their healthcare provider.

Grade ≥3 increases in alanine aminotransferase (ALT) (6% versus 2%) and aspartate aminotransferase (AST) (3% versus 1%) were reported in the Verzenio and placebo arms, respectively, in MONARCH 3. Grade ≥3 increases in ALT (4% versus 2%) and AST (2% versus 3%) were reported in the Verzenio and placebo arms respectively, in MONARCH 2.

In MONARCH 3, for patients receiving Verzenio plus an aromatase inhibitor with Grade ≥3 increases in ALT or AST, median time to onset was 61 and 71 days, respectively, and median time to resolution to Grade <3 was 14 and 15 days, respectively. In MONARCH 2, for patients receiving Verzenio plus fulvestrant with Grade ≥3 increases in ALT or AST, median time to onset was 57 and 185 days, respectively, and median time to resolution to Grade <3 was 14 and 13 days, respectively.

For assessment of potential hepatotoxicity, monitor liver function tests (LFTs) prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, dose discontinuation, or delay in starting treatment cycles is recommended for patients who develop persistent or recurrent Grade 2, or Grade 3 or 4, hepatic transaminase elevation.

Venous thromboembolic events were reported in 5% of patients treated with Verzenio plus an aromatase inhibitor as compared to 0.6% of patients treated with an aromatase inhibitor plus placebo in MONARCH 3. Venous thromboembolic events were reported in 5% of patients treated with Verzenio plus fulvestrant in MONARCH 2 as compared to 0.9% of patients treated with fulvestrant plus placebo. Venous thromboembolic events included deep vein thrombosis, pulmonary embolism, pelvic venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior vena cava thrombosis. Across the clinical development program, deaths due to venous thromboembolism have been reported. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate.

Verzenio can cause fetal harm when administered to a pregnant woman based on findings from animal studies and the mechanism of action. In animal reproduction studies, administration of abemaciclib to pregnant rats during the period of organogenesis caused teratogenicity and decreased fetal weight at maternal exposures that were similar to the human clinical exposure based on area under the curve (AUC) at the maximum recommended human dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Verzenio and for at least 3 weeks after the last dose. There are no data on the presence of Verzenio in human milk or its effects on the breastfed child or on milk production. Advise lactating women not to breastfeed during Verzenio treatment and for at least 3 weeks after the last dose because of the potential for serious adverse reactions in breastfed infants. Based on findings in animals, Verzenio may impair fertility in males of reproductive potential.

The most common adverse reactions (all grades, ≥10%) observed in MONARCH 3 for Verzenio plus anastrozole or letrozole and ≥2% higher than placebo plus anastrozole or letrozole vs placebo plus anastrozole or letrozole were diarrhea (81% vs 30%), neutropenia (41% vs 2%), fatigue (40% vs 32%), infections (39% vs 29%), nausea (39% vs 20%), abdominal pain (29% vs 12%), vomiting (28% vs 12%), anemia (28% vs 5%), alopecia (27% vs 11%), decreased appetite (24% vs 9%), leukopenia (21% vs 2%), creatinine increased (19% vs 4%), constipation (16% vs 12%), ALT increased (16% vs 7%), AST increased (15% vs 7%), rash (14% vs 5%), pruritus (13% vs 9%), cough (13% vs 9%), dyspnea (12% vs 6%), dizziness (11% vs 9%), weight decreased (10% vs 3%), influenza-like illness (10% vs 8%), and thrombocytopenia (10% vs 2%).

The most common adverse reactions (all grades, ≥10%) observed in MONARCH 2 for Verzenio plus fulvestrant and ≥2% higher than placebo plus fulvestrant vs placebo plus fulvestrant were diarrhea (86% vs 25%), neutropenia (46% vs 4%), fatigue (46% vs 32%), nausea (45% vs 23%), infections (43% vs 25%), abdominal pain (35% vs 16%), anemia (29% vs 4%), leukopenia (28% vs 2%), decreased appetite (27% vs 12%), vomiting (26% vs 10%), headache (20% vs 15%), dysgeusia (18% vs 3%), thrombocytopenia (16% vs 3%), alopecia (16% vs 2%), stomatitis (15% vs 10%), ALT increased (13% vs 5%), pruritus (13% vs 6%), cough (13% vs 11%), dizziness (12% vs 6%), AST increased (12% vs 7%), peripheral edema (12% vs 7%), creatinine increased (12% vs <1%), rash (11% vs 4%), pyrexia (11% vs 6%), and weight decreased (10% vs 2%).

The most common adverse reactions (all grades, ≥10%) observed in MONARCH 1 with Verzenio were diarrhea (90%), fatigue (65%), nausea (64%), decreased appetite (45%), abdominal pain (39%), neutropenia (37%), vomiting (35%), infections (31%), anemia (25%), thrombocytopenia (20%), headache (20%), cough (19%), leukopenia (17%), constipation (17%), arthralgia (15%), dry mouth (14%), weight decreased (14%), stomatitis (14%), creatinine increased (13%), alopecia (12%), dysgeusia (12%), pyrexia (11%), dizziness (11%), and dehydration (10%).

The most frequently reported ≥5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 3 were neutropenia (22% vs 2%), diarrhea (9% vs 1%), leukopenia (8% vs <1%), ALT increased (7% vs 2%), and anemia (6% vs 1%).

The most frequently reported ≥5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 2 were neutropenia (27% vs 2%), diarrhea (13% vs <1%), leukopenia (9% vs 0%), anemia (7% vs 1%), and infections (6% vs 3%).

The most frequently reported ≥5% Grade 3 or 4 adverse reactions from MONARCH 1 with Verzenio were neutropenia (24%), diarrhea (20%), fatigue (13%), infections (7%), leukopenia (6%), anemia (5%), and nausea (5%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 3 in ≥10% for Verzenio plus anastrozole or letrozole and ≥2% higher than placebo plus anastrozole or letrozole vs placebo plus anastrozole or letrozole were increased serum creatinine (98% vs 84%; 2% vs 0%), decreased white blood cells (82% vs 27%; 13% vs <1%), anemia (82% vs 28%; 2% vs 0%), decreased neutrophil count (80% vs 21%; 22% vs 3%), decreased lymphocyte count (53% vs 26%; 8% vs 2%), decreased platelet count (36% vs 12%; 2% vs <1%), increased ALT (48% vs 25%; 7% vs 2%), and increased AST (37% vs 23%; 4% vs <1%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 2 in ≥10% for Verzenio plus fulvestrant and ≥2% higher than placebo plus fulvestrant vs placebo plus fulvestrant were increased serum creatinine (98% vs 74%; 1% vs 0%), decreased white blood cells (90% vs 33%; 23% vs 1%), decreased neutrophil count (87% vs 30%; 33% vs 4%), anemia (84% vs 33%; 3% vs <1%), decreased lymphocyte count (63% vs 32%; 12% vs 2%), decreased platelet count (53% vs 15%; 2% vs 0%), increased ALT (41% vs 32%; 5% vs 1%), and increased AST (37% vs 25%; 4% vs 4%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 1 with Verzenio were increased serum creatinine (98%; <1%), decreased white blood cells (91%; 28%), decreased neutrophil count (88%; 27%), anemia (68%; 0%), decreased lymphocyte count (42%; 14%), decreased platelet count (41%; 2%), increased ALT (31%; 3%), and increased AST (30%; 4%).

Strong CYP3A inhibitors increased the exposure of abemaciclib plus its active metabolites to a clinically meaningful extent and may lead to increased toxicity. Avoid concomitant use of ketoconazole. Ketoconazole is predicted to increase the AUC of abemaciclib by up to 16-fold. In patients with recommended starting doses of 200 mg twice daily or 150 mg twice daily, reduce the Verzenio dose to 100 mg twice daily with concomitant use of other strong CYP3A inhibitors. In patients who have had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the Verzenio dose to 50 mg twice daily with concomitant use of other strong CYP3A inhibitors. If a patient taking Verzenio discontinues a strong CYP3A inhibitor, increase the Verzenio dose (after 3 to 5 half-lives of the inhibitor) to the dose that was used before starting the strong inhibitor. Patients should avoid grapefruit products.

Avoid concomitant use of strong CYP3A inducers and consider alternative agents. Coadministration of Verzenio with rifampin, a strong CYP3A inducer, decreased the plasma concentrations of abemaciclib plus its active metabolites and may lead to reduced activity.

With severe hepatic impairment (Child-Pugh Class C), reduce the Verzenio dosing frequency to once daily. The pharmacokinetics of Verzenio in patients with severe renal impairment (CLcr <30 mL/min), end stage renal disease, or in patients on dialysis is unknown. No dosage adjustments are necessary in patients with mild or moderate hepatic (Child-Pugh A or B) and/or renal impairment (CLcr ≥30-89 mL/min).

Please see full Prescribing.Information for Verzenio.

AL HCP ISI 26FEB2018