See how HR+, HER2- MBC can take a different course

Watch MBC in Motion

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HR+, HER2- Metastatic breast cancer (MBC) doesn't stay still.

HER2-=human epidermal growth factor receptor 2–negative; HR+=hormone receptor–positive.

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SOME WOMEN DEVELOP VISCERAL DISEASE*

*Visceral disease: ≥1 lesion on an internal organ or in the third space (including lung, liver, pleural, or peritoneal metastatic involvement).1

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WHERE CANCER

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CAN SPREAD TO

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THE LIVER

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OR THE LUNGS1,2

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WOMEN WITH VISCERAL DISEASE2-5,7*

*Visceral disease: ≥1 lesion on an internal organ or in the third space (including lung, liver, pleural, or peritoneal metastatic involvement).1

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ARE AT A HIGHER RISK OF PROGRESSION OR DEATH2-5,7†

Patients with disease progression following ET who were at “higher risk” (defined as the presence of visceral disease or primary ET resistance§, which are associated with decreased mOS) were included in the MONARCH 2 clinical trial.2-6

Visceral disease: ≥1 lesion on an internal organ or in the third space (including lung, liver, pleural, or peritoneal metastatic involvement).1
§Primary resistance: relapse within the first 2 years of adjuvant ET or progressive disease within the first 6 months of first-line ET for MBC.7
ET=endocrine therapy; mOS=median overall survival.

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BUT IT’S NOT JUST VISCERAL DISEASE THAT’S LINKED TO HIGHER RISK2-5†

Patients with disease progression following ET who were at “higher risk” (defined as the presence of visceral disease or primary ET resistance§, which are associated with decreased mOS) were included in the MONARCH 2 clinical trial.2-6

Visceral disease: ≥1 lesion on an internal organ or in the third space (including lung, liver, pleural, or peritoneal metastatic involvement).1

§Primary resistance: relapse within the first 2 years of adjuvant ET or progressive disease within the first 6 months of first-line ET for MBC.7

ET=endocrine therapy; mOS=median overall survival.

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SOME HR+, HER2- MBC TAKES A DIFFERENT COURSE

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WHERE ENDOCRINE THERAPY IS MET WITH

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PRIMARY RESISTANCE§

§Primary resistance: relapse within the first 2 years of adjuvant ET or progressive disease within the first 6 months of first-line ET for MBC.7

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WHICH ALLOWS CANCER TO PROGRESS FASTER

§Primary resistance: relapse within the first 2 years of adjuvant ET or progressive disease within the first 6 months of first-line ET for MBC.7

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AND LEADS TO HIGHER RISK7†

Patients with disease progression following ET who were at “higher risk” (defined as the presence of visceral disease‡ or primary ET resistance§, which are associated with decreased mOS) were included in the MONARCH 2 clinical trial.2-6

Visceral disease: ≥1 lesion on an internal organ or in the third space (including lung, liver, pleural, or peritoneal metastatic involvement).1

§Primary resistance: relapse within the first 2 years of adjuvant ET or progressive disease within the first 6 months of first-line ET for MBC.7

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FOR WOMEN WITH HR+, HER2- MBC WITH VISCERAL DISEASE OR PRIMARY ENDOCRINE THERAPY RESISTANCE

Patients with disease progression following ET who were at “higher risk” (defined as the presence of visceral disease‡ or primary ET resistance§, which are associated with decreased mOS) were included in the MONARCH 2 clinical trial.2-6

Visceral disease: ≥1 lesion on an internal organ or in the third space (including lung, liver, pleural, or peritoneal metastatic involvement).1

§Primary resistance: relapse within the first 2 years of adjuvant ET or progressive disease within the first 6 months of first-line ET for MBC.7

[The bubbles settle.]

CAN MORE BE DONE?

Patients with disease progression following ET who were at “higher risk” (defined as the presence of visceral disease‡ or primary ET resistance§, which are associated with decreased mOS) were included in the MONARCH 2 clinical trial.2-6

Visceral disease: ≥1 lesion on an internal organ or in the third space (including lung, liver, pleural, or peritoneal metastatic involvement).1

§Primary resistance: relapse within the first 2 years of adjuvant ET or progressive disease within the first 6 months of first-line ET for MBC.7

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LEARN ABOUT VERZENIO FOR WOMEN WITH HR+, HER2- MBC, INCLUDING THOSE AT HIGHER RISK2,7†

Patients with disease progression following ET who were at “higher risk” (defined as the presence of visceral disease‡ or primary ET resistance§, which are associated with decreased mOS) were included in the MONARCH 2 clinical trial.2-6

Visceral disease: ≥1 lesion on an internal organ or in the third space (including lung, liver, pleural, or peritoneal metastatic involvement).1

§Primary resistance: relapse within the first 2 years of adjuvant ET or progressive disease within the first 6 months of first-line ET for MBC.7

Verzenio® (abemaciclib) 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.7

Please see the adjacent Important Safety Information and Prescribing Information for Verzenio

[Verzenio logo]

VERZENIODATA.com

Please see the adjacent Important Safety Information and Prescribing Information for Verzenio

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SELECT 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.

The labeling for Verzenio contains warnings and precautions for diarrhea, neutropenia, interstitial lung disease (ILD)/pneumonitis, 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 ILD/pneumonitis, thrombosis, 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.

The most common adverse reactions (all grades, ≥20%) observed in MONARCH 2 for Verzenio 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%), and headache (20% vs 15%).

Please see the adjacent Important Safety Information and Prescribing Information for Verzenio

[Water is still. References enter on screen.]

References
1. Data on file. Lilly USA, LLC. ONC20171128a. 2. Sledge GW Jr, Toi M, Neven P, et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2-negative breast cancer that progressed on endocrine therapy—MONARCH 2: a randomized clinical trial [published online September 29, 2019]. JAMA Oncol. 2020;6(1):116-124. doi:10.1001/jamaoncol.2019.4782. 3. Yamamura J, Kamigaki S, Fujita J, Osato H, Komoike Y. The difference in prognostic outcomes between de novo stage IV and recurrent metastatic patients with hormone receptor-positive, HER2-negative breast cancer. In Vivo. 2018;32(2):353-358. 4. Gong Y, Liu Y-R, Ji P, Hu X, Shao ZM. Impact of molecular subtypes on metastatic breast cancer patients: a SEER population-based study. Sci Rep. 2017;7:45411. 5. Wang R, Zhu Y, Liu X, Liao X, He J, Niu L. The clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer. BMC Cancer. 2019;19(1):1091. 6. 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(25):2875-2884. 7. Verzenio [package insert]. Indianapolis, IN: Eli Lilly and Company; 2020.

PP-AL-US-2471 12/2020 ©Lilly USA, LLC 2020. All rights reserved.

Verzenio® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries or affiliates.

Indication & Important Safety Information
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)1:

  • 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.

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with Verzenio and other CDK4/6 inhibitors. Across clinical trials (MONARCH 1, MONARCH 2, MONARCH 3), 3.3% of Verzenio-treated patients had ILD/pneumonitis of any grade, 0.6% had Grade 3 or 4, and 0.4% had fatal outcomes. Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported.

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. Symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded by means of appropriate investigations.

Dose interruption or dose reduction is recommended in patients who develop persistent or recurrent Grade 2 ILD/pneumonitis. Permanently discontinue Verzenio in all patients with grade 3 or 4 ILD/pneumonitis.

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 and moderate 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 the strong CYP3A inhibitor 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 strong CYP3A inhibitors other than ketoconazole. 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 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 inhibitor. With concomitant use of moderate CYP3A inhibitors, monitor for adverse reactions and consider reducing the Verzenio dose in 50 mg decrements. Patients should avoid grapefruit products.

Avoid concomitant use of strong or moderate CYP3A inducers and consider alternative agents. Coadministration of strong or moderate CYP3A inducers 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 17SEP2019

Reference: 1. Verzenio [package insert]. Indianapolis, IN: Eli Lilly and Company; 2020.