INDIANAPOLIS, Oct. 14, 2021 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) today announced updated data from the positive
Phase 3 monarchE trial evaluating the investigational use of
Verzenio® (abemaciclib) in combination with standard
adjuvant endocrine therapy (ET) for the treatment of hormone
receptor-positive (HR+), human epidermal growth factor receptor
2-negative (HER2-), node-positive, high risk early breast cancer
(EBC). These data were presented at today's ESMO Virtual Plenary
and simultaneously published in the Annals of
Oncology.
As previously published in the Journal of Clinical
Oncology,1 monarchE met its primary endpoint of
a statistically significant improvement in invasive disease-free
survival (IDFS) in the intent-to-treat (ITT) population for
patients treated with adjuvant Verzenio plus ET
compared to those treated with ET alone. Consistent with
expert guidelines, IDFS was defined as the length of time
before breast cancer comes back, any new cancer
develops, or death.
The trial included women and men with HR+ HER2-, node-positive
EBC who had a high risk of disease recurrence based on clinical and
pathological features (N=5,637). Patients were assigned to one
of two cohorts. Cohort 1 enrolled patients with ≥4 positive
axillary lymph nodes (ALN), or 1-3 positive ALN and either Grade 3
disease or tumor size ≥5 cm. Cohort 2 enrolled patients with 1-3
positive ALN and centrally determined Ki-67 score of ≥20% (defined
in the study as "Ki-67 high"). Ki-67 is a marker of cellular
proliferation. Ki-67 score was also determined centrally in Cohort
1 patients with a suitable sample, but Ki-67 determination was not
required for enrollment in this cohort. The ITT population included
both Cohort 1 and Cohort 2.
Data in today's presentation and publication include updated
results reflecting median follow-up of 27 months. In the updated
analysis, the benefit of Verzenio on IDFS and distant relapse-free
survival (DRFS) was maintained (Table 1 below). At three years, the
absolute improvement rates in IDFS and DRFS were 5.4% and 4.2%,
respectively. Exploratory piecewise analyses of the IDFS and DRFS
hazard ratio (HR) estimates within each year were also conducted,
which demonstrated increasing magnitude of IDFS effect size over
time: from the first year (0-1yr HR = 0.80, 95% CI: 0.59, 1.03) to
the second year (1-2yr HR = 0.68, 95% CI: 0.52, 0.87), and
strengthened beyond the two-year study treatment period (2+yr HR =
0.60, 95% CI: 0.40, 0.86). Similarly, the DRFS HR estimates
strengthened from the first year (0-1yr HR = 0.73, 95% CI: 0.52,
0.99) to the second year (1-2yr HR = 0.68, 95% CI: 0.51, 0.88), and
persisted beyond the two-year study treatment period (2+yr HR =
0.69, 95% CI: 0.45, 1.03). The impact of Ki-67 score on prognosis
and likelihood of benefit from Verzenio was also analyzed. As
expected, a high Ki-67 score of ≥20% was prognostic of increased
recurrence risk among patients with high-risk clinical and
pathological features. However, Verzenio conferred consistent
benefit in reducing risk of recurrence regardless of having a low
(<20%) or high (≥20%) Ki-67 score among patients with high-risk
clinical and pathological features (Table 2 below). With 90 percent
of patients now having completed the two-year treatment period or
discontinued early, safety data are considered mature and remain
consistent with the known profile of Verzenio. All patients in
monarchE will continue to be followed to assess overall survival
and other endpoints. Overall survival data were not yet mature.
"The results from monarchE are truly impressive and we are
encouraged by the consistency of the treatment benefit and
increasing magnitude of effect observed over time in reducing the
risk of recurrence and development of metastatic disease," said
Joyce A. O'Shaughnessy, M.D.,
Celebrating Women Chair in Breast Cancer Research, Baylor University Medical Center, Texas Oncology, US Oncology,
Dallas Texas, monarchE
investigator and presenter at today's ESMO Virtual Plenary. "These
data suggest that the addition of adjuvant Verzenio to endocrine
therapy in the high risk early breast cancer setting has the
potential to change the way we treat these patients and may address
a significant unmet need for those with clinical and pathological
risk features who are in need of new treatment options."
The following table shows the evolution of IDFS and DRFS data in
the ITT population.
Table 1.
|
Primary
Outcome1
|
Additional
Follow-Up
|
Data cut-off
date
|
July 8,
2020
|
April 1,
2021
|
Patients off study
treatment period
|
41.0%
|
89.6%
|
Efficacy
Results
|
Verzenio +
ET
|
ET
alone
|
Verzenio +
ET
|
ET
alone
|
Median follow-up,
months
|
19.1
|
27.1
|
Invasive
disease-free survival (IDFS)
|
Events,
n
|
163
|
232
|
232
|
333
|
IDFS rates, % (95%
CI)
|
|
|
|
|
2-year
|
92.3 (90.9,
93.5)
|
89.3 (87.7,
90.7)
|
92.7 (91.6,
93.6)
|
90.0 (88.8,
91.1)
|
3-year
|
Not
estimable
|
Not
estimable
|
88.8 (87.0,
90.3)
|
83.4 (81.3,
85.3)
|
HR (95%
CI)
p-value
|
0.71 (0.58,
0.87)
*Nominal p-value
= 0.0009
|
0.70 (0.59,
0.82)
*Nominal p-value
<0.0001
|
Distant
relapse-free survival (DRFS)
|
Events,
n
|
131
|
193
|
191
|
278
|
DRFS rates, % (95%
CI)
|
|
|
|
|
2-year
|
93.8 (92.6,
94.9)
|
90.8 (89.3,
92.1)
|
94.1 (93.2,
95.0)
|
91.6 (90.5,
92.6)
|
3-year
|
Not
estimable
|
Not
estimable
|
90.3 (88.6,
91.8)
|
86.1 (84.2,
87.9)
|
HR (95%
CI)
|
0.69 (0.55,
0.86)
|
0.69 (0.57,
0.83)
|
1 Johnston
SRD, Harbeck N, Hegg R, et al; monarchE Committee Members and
Investigators. Abemaciclib combined with endocrine therapy for the
adjuvant treatment of HR+, HER2-, node-positive, high-risk, early
breast cancer (monarchE) [published online ahead of print,
September 20, 2020]. J Clin Oncol.
doi:10.1200/JCO.20.02514.
|
|
*The primary efficacy
endpoint was statistically significant at interim analysis
2
|
The following table shows IDFS in Cohort 1 according to
centrally determined Ki-67 score [low (<20%), high (≥20%)].*
Table 2.
|
Verzenio +
ET
|
ET
alone
|
HR (95%
CI)
|
Cohort 1 Ki-67
High, N = 2003
|
Patients,
N
|
1017
|
986
|
0.626
(0.488,
0.803)
|
Events,
n
|
104
|
158
|
3-Year IDFS
Rates
|
86.1%
|
79.0%
|
Cohort 1 Ki-67
Low, N = 1914
|
Patients,
N
|
946
|
968
|
0.704
(0.506,
0.979)
|
Events,
n
|
62
|
86
|
3-Year IDFS
Rates
|
91.7%
|
87.2%
|
*Data from Additional
Follow-up analysis with a data cut-off date of April 1,
2021
|
"We are extremely pleased with the consistency of the landmark
results from monarchE and are excited to see these important data
shared with the breast cancer community," said David Hyman, M.D., chief medical officer,
oncology at Lilly. "Verzenio treatment benefit observed at the
primary outcome analysis was maintained with 27 months of median
follow-up, including beyond the Verzenio treatment period,
reinforcing our confidence in the observed treatment effect."
Adverse reactions from monarchE were consistent with the known
safety profile for Verzenio.1 A higher incidence of
Grade ≥3 adverse events (AEs) and serious adverse events was
observed with Verzenio plus ET compared to ET alone (50% vs. 16%
and 15% vs. 9%, respectively). The most frequent AEs were diarrhea,
neutropenia, and fatigue in the Verzenio plus ET arm, and
arthralgia, hot flush, and fatigue in the ET alone arm.
About the monarchE Study
monarchE is a global, randomized, open-label, two cohort,
multicenter Phase 3 study in adult women and men with HR+ HER2-,
node-positive resected EBC with clinical and pathological features
consistent with a high risk of disease recurrence. A total of 5,637
patients were randomized (1:1) to receive two years of Verzenio 150
mg twice daily plus physician's choice of standard endocrine
therapy, or standard endocrine therapy alone. Patients in both
treatment arms were instructed to continue to receive adjuvant
endocrine therapy for up to 5-10 years as recommended by their
clinician. Cohort 1 enrolled patients with ≥4 positive axillary
lymph nodes (ALN), or 1-3 positive ALN and either Grade 3 disease
or tumor size ≥5 cm. Cohort 2 enrolled patients with 1-3 positive
ALN and centrally determined Ki-67 score of ≥20%. The primary
endpoint was IDFS in the ITT population (Cohorts 1 & 2).
Secondary endpoints were IDFS in patients with high Ki-67 score (in
the ITT population and in the Cohort 1 population), DRFS, overall
survival, and safety.1,2
About Early Breast Cancer and Risk of Recurrence
It is
estimated that 90 percent of all breast cancers are detected at an
early stage. Although the prognosis for HR+ HER2- EBC is generally
positive, 20 percent of patients will experience recurrence
potentially to incurable metastatic disease.3 Risk
of recurrence is greatest within the initial two to three years
post-diagnosis, particularly in patients with node-positive, high
risk EBC.4 Factors associated with high risk of
recurrence include: positive nodal status, large tumor size (≥5
cm), high tumor grade (Grade 3), and high rate of cellular
proliferation [Ki-67 score (≥20%)].2
Node-positive means that cancer cells from the tumor in the
breast have been found in the lymph nodes in the armpit area.
Although the breast cancer is removed through surgery, the presence
of cancer cells in the lymph nodes signifies that there is a higher
chance of the cancer returning and spreading.
About Breast Cancer
Breast cancer has now surpassed
lung cancer as the most commonly diagnosed cancer worldwide,
according to GLOBOCAN. The estimated 2.3 million new cases indicate
that 1 in every 8 cancers diagnosed in 2020 is breast cancer. With
approximately 685,000 deaths in 2020, breast cancer is the
fifth-leading cause of cancer death worldwide.5 In the
U.S., it is estimated that there will be 281,550 new cases of
breast cancer in 2021.6
Approximately 70 percent of all breast cancers are of the HR+
HER2- subtype.6
About Verzenio® (abemaciclib)
Verzenio® abemaciclib is a targeted treatment known
as a CDK4/6 inhibitor. Verzenio is a non-chemotherapy oral
tablet.
Verzenio works inside the cell to block CDK4/6 activity and help
stop the growth of cancer cells, so they may eventually die (based
on preclinical studies).* Cyclin-dependent kinases (CDK)4/6 are
activated by binding to D-cyclins. In estrogen receptor-positive
(ER+) breast cancer cell lines, cyclin D1 and CDK4/6 promote
phosphorylation of the retinoblastoma protein (Rb), cell cycle
progression, and cell proliferation.
In vitro, continuous exposure to Verzenio inhibited Rb
phosphorylation and blocked progression from G1 to S phase of the
cell cycle, resulting in senescence and apoptosis (cell death).
Preclinically, Verzenio dosed daily without interruption resulted
in reduction of tumor size. Inhibiting CDK4/6 in healthy cells can
result in side effects, some of which may be serious. Clinical
evidence also suggests that Verzenio crosses the blood-brain
barrier. In patients with advanced cancer, including breast cancer,
concentrations of Verzenio and its active metabolites (M2 and M20)
in cerebrospinal fluid are comparable to unbound plasma
concentrations.
Verzenio is Lilly's first solid oral dosage form to be made
using a faster, more efficient process known as continuous
manufacturing. Continuous manufacturing is a new and advanced type
of manufacturing within the pharmaceutical industry, and Lilly is
one of the first companies to use this technology.
INDICATIONS FOR VERZENIO
Verzenio® (abemaciclib) in combination with endocrine
therapy (ET) is indicated for the adjuvant treatment of adult
patients with hormone receptor-positive (HR+), human epidermal
growth factor receptor 2-negative (HER2-), node-positive, early
breast cancer (EBC) at high risk of recurrence and a Ki-67 score of
≥20% as determined by an FDA-approved test.
Verzenio is indicated for the treatment of HR+ HER2- advanced or
metastatic breast cancer:
- in combination with an aromatase inhibitor for postmenopausal
women, and men, as initial endocrine-based therapy
- in combination with fulvestrant for adult patients with disease
progression following endocrine therapy
- as a single agent for adult patients with disease progression
following endocrine therapy and prior chemotherapy in the
metastatic setting
IMPORTANT SAFETY INFORMATION FOR VERZENIO
(abemaciclib)
Severe diarrhea associated with dehydration and
infection occurred in patients treated with
Verzenio. Across four clinical trials in 3691
patients, diarrhea occurred in 81 to 90% of
patients who received Verzenio. Grade 3 diarrhea occurred in 8 to
20% of patients receiving Verzenio. Most patients experienced
diarrhea during the first month of Verzenio treatment. The
median time to onset of the first diarrhea event ranged from 6 to 8
days; and the median duration of Grade 2 and Grade 3 diarrhea
ranged from 6 to 11 days and 5 to 8 days, respectively. Across
trials, 19 to 26% of patients with diarrhea required a Verzenio
dose interruption and 13 to 23% required a dose reduction.
Instruct patients to start antidiarrheal therapy, such as
loperamide, at the first sign of loose stools, 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, including febrile neutropenia and fatal
neutropenic sepsis, occurred in patients treated with Verzenio.
Across four clinical trials in 3691 patients, neutropenia occurred
in 37 to 46% of patients receiving Verzenio. A Grade ≥3 decrease in
neutrophil count (based on laboratory findings) occurred in 19 to
32% of patients receiving Verzenio. Across trials, the median
time to first episode of Grade ≥3 neutropenia ranged from 29 to 33
days, and the median duration of Grade ≥3 neutropenia ranged from
11 to 16 days. Febrile neutropenia has been reported in <1% of
patients exposed to Verzenio across trials. Two deaths due to
neutropenic sepsis were observed in MONARCH 2. Inform patients to
promptly report any episodes of fever to their healthcare
provider.
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.
Severe, life-threatening, or fatal interstitial lung disease
(ILD) or pneumonitis can occur in patients treated with
Verzenio and other CDK4/6 inhibitors. In Verzenio-treated
patients in EBC (monarchE), 3% of patients experienced ILD or
pneumonitis of any grade: 0.4% were Grade 3 or 4 and there was one
fatality (0.1%). In Verzenio-treated patients in MBC (MONARCH 1,
MONARCH 2, MONARCH 3), 3.3% of Verzenio-treated patients had ILD or
pneumonitis of any grade: 0.6% had Grade 3 or 4, and 0.4% had fatal
outcomes. Additional cases of ILD or pneumonitis have been observed
in the postmarketing setting, with fatalities reported.
Monitor patients for pulmonary symptoms indicative of ILD or
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 or pneumonitis. Permanently discontinue
Verzenio in all patients with Grade 3 or 4 ILD or pneumonitis.
Grade ≥3 increases in alanine aminotransferase
(ALT) (2 to 6%) and aspartate aminotransferase
(AST) (2 to 3%) were reported in patients receiving
Verzenio. Across three clinical trials in 3559 patients (monarchE,
MONARCH 2, MONARCH 3), the median time to onset of Grade ≥3 ALT
increases ranged from 57 to 87 days and the median time to
resolution to Grade <3 was 13 to 14 days. The median time to
onset of Grade ≥3 AST increases ranged from 71 to 185 days and the
median time to resolution to Grade <3 ranged from 11 to 15
days.
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 any Grade 3 or 4 hepatic transaminase
elevation.
Venous thromboembolic events (VTE) were reported in
2 to 5% of patients across three clinical trials in 3559 patients
treated with Verzenio (monarchE, MONARCH 2, MONARCH 3). VTE
included deep vein thrombosis, pulmonary embolism, pelvic
venous thrombosis, cerebral venous sinus thrombosis, subclavian and
axillary vein thrombosis, and inferior vena cava thrombosis. In
clinical trials, deaths due to VTE have been reported in patients
treated with Verzenio.
Verzenio has not been studied in patients with early breast
cancer who had a history of VTE. Monitor patients for signs and
symptoms of venous thrombosis and pulmonary embolism and treat as
medically appropriate. Dose interruption is recommended for EBC
patients with any grade VTE and for MBC patients with a Grade 3 or
4 VTE.
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 3 weeks after the last dose.
Based on findings in animals, Verzenio may impair fertility in
males of reproductive potential. 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.
The most common adverse reactions (all grades,
≥10%) observed in monarchE for Verzenio plus
tamoxifen or an aromatase inhibitor vs tamoxifen or an
aromatase inhibitor, with a difference between arms of
≥2%, were diarrhea (84% vs 9%), infections (51% vs 39%),
neutropenia (46% vs 6%), fatigue (41% vs 18%),
leukopenia (38% vs 7%), nausea (30% vs 9%), anemia (24% vs
4%), headache (20% vs 15%), vomiting (18% vs 4.6%),
stomatitis (14% vs 5%), lymphopenia (14% vs 3%), thrombocytopenia
(13% vs 2%), decreased appetite (12% vs 2.4%), ALT increased (12%
vs 6%), AST increased (12% vs 5%), dizziness (11% vs 7%), rash (11%
vs 4.5%), and alopecia (11% vs 2.7 %).
The most frequently reported ≥5% Grade 3 or 4
adverse reaction that occurred in the Verzenio arm vs the
tamoxifen or an aromatase inhibitor arm of monarchE were
neutropenia (19.6% vs 1%), leukopenia (11% vs <1%), diarrhea (8%
vs 0.2%), and lymphopenia (5% vs <1%).
Lab abnormalities (all grades; Grade 3 or 4) for
monarchE in ≥10% for Verzenio plus tamoxifen or an
aromatase inhibitor with a difference between arms
of ≥2% were increased serum creatinine (99% vs
91%; .5% vs <.1%), decreased white blood cells (89% vs 28%;
19.1% vs 1.1%), decreased neutrophil count (84% vs 23%; 18.7% vs
1.9%), anemia (68% vs 17%; 1% vs .1%), decreased lymphocyte count
(59% vs 24%; 13.2 % vs 2.5%), decreased platelet count (37% vs 10%;
.9% vs .2%), increased ALT (37% vs 24%; 2.6% vs 1.2%), increased
AST (31% vs 18%; 1.6% vs .9%), and hypokalemia (11% vs 3.8%; 1.3%
vs 0.2%).
The most common adverse reactions (all grades,
≥10%) observed in MONARCH 3 for Verzenio plus anastrozole
or letrozole vs anastrozole or letrozole, with a difference
between arms of ≥2%, were diarrhea (81% vs 30%), fatigue
(40% vs 32%), neutropenia (41% vs 2%), 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 3.1%), influenza-like illness (10% vs
8%), and thrombocytopenia (10% vs 2%).
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 1%), diarrhea (9% vs 1.2%), leukopenia (7% vs
<1%)), increased ALT (6% vs 2%), and anemia (6% vs 1%).
Lab abnormalities (all grades; Grade 3 or 4) for
MONARCH 3 in ≥10% for Verzenio plus anastrozole or
letrozole with a difference between arms of
≥2% were increased serum creatinine (98% vs
84%; 2.2% vs 0%), decreased white blood cells (82% vs 27%; 13% vs
0.6%), anemia (82% vs 28%; 1.6% vs 0%), decreased neutrophil count
(80% vs 21%; 21.9% vs 2.6%), decreased lymphocyte count (53% vs
26%; 7.6% vs 1.9%), decreased platelet count (36% vs 12%; 1.9% vs
0.6%), increased ALT (48% vs 25%; 6.6% vs 1.9%), and increased AST
(37% vs 23%; 3.8% vs 0.6%).
The most common adverse reactions (all grades,
≥10%) observed in MONARCH 2 for Verzenio plus
fulvestrant vs fulvestrant, with a difference between arms
of ≥2%, 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 2.7%),
thrombocytopenia (16% vs 3%), alopecia (16% vs 1.8%), 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 4.5%), pyrexia (11% vs 6%), and weight
decreased (10% vs 2.2%).
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 (25% vs 1%), diarrhea (13% vs 0.4%), leukopenia (9% vs
0%), anemia (7% vs 1%), and infections (5.7% vs
3.5%).
Lab abnormalities (all grades; Grade 3 or 4) for
MONARCH 2 in ≥10% for Verzenio plus fulvestrant with a
difference between arms of ≥2% were increased serum
creatinine (98% vs 74%; 1.2% vs 0%), decreased white blood cells
(90% vs 33%; 23.7% vs .9%), decreased neutrophil count (87% vs 30%;
32.5% vs 4.2%), anemia (84% vs 34%; 2.6% vs .5%), decreased
lymphocyte count (63% vs 32%; 12.2% vs 1.8%), decreased platelet
count (53% vs 15%; 2.1% vs 0%), increased ALT (41% vs 32%; 4.6% vs
1.4%), and increased AST (37% vs 25%; 3.9% vs 4.2%).
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%), constipation
(17%), leukopenia (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 from MONARCH 1 with Verzenio were
diarrhea (20%), neutropenia (24%), fatigue (13%), and leukopenia
(5%).
Lab abnormalities (all grades; Grade 3 or 4) for
MONARCH 1 with Verzenio were increased serum creatinine
(99%; .8%), decreased white blood cells (91%; 28%), decreased
neutrophil count (88%; 26.6%), anemia (69%; 0%), decreased
lymphocyte count (42%; 13.8%), decreased platelet count (41%;
2.3%), increased ALT (31%; 3.1%), and increased AST (30%;
3.8%).
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 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 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 12OCT2021
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© Lilly USA, LLC 2021. ALL
RIGHTS RESERVED.
Verzenio® is a trademark owned by or licensed to Eli
Lilly and Company, its subsidiaries, or affiliates.
This press release contains forward-looking statements (as
that term is defined in the Private Securities Litigation Reform
Act of 1995) about Verzenio (abemaciclib) as a treatment for
patients with early breast cancer and reflects Lilly's current
beliefs and expectations. However, as with any pharmaceutical
product, there are substantial risks and uncertainties in the
process of development and commercialization. Among other things,
there can be no guarantee that future study results will be
consistent with the results to date or that Verzenio will receive
additional regulatory approvals or be commercially successful. For
further discussion of these and other risks and uncertainties, see
Lilly's most recent Form 10-K and Form 10-Q filings with the United
States Securities and Exchange Commission. Except as required by
law, Lilly undertakes no duty to update forward-looking statements
to reflect events after the date of this release.
1 Johnston SRD, Harbeck N, Hegg R, et al; monarchE
Committee Members and Investigators. Abemaciclib combined with
endocrine therapy for the adjuvant treatment of HR+, HER2-,
node-positive, high-risk, early breast cancer (monarchE) [published
online ahead of print, September 20,
2020]. J Clin Oncol. doi:10.1200/JCO.20.02514.
2 Verzenio [package insert]. Indianapolis, IN: Eli Lilly and Company.
3 Early Breast Cancer Trialists' Collaborative Group
(EBCTCG). Effects of chemotherapy and hormonal therapy for early
breast cancer on recurrence and 15-year survival: an overview of
the randomised trials. Lancet. 2005;365(9472):1687-1717.
doi:10.1016/S0140-6736(05)66544-0.
4 Cheng L, Swartz MD, Zhao H, et al. Hazard of
recurrence among women after primary breast cancer treatment--a
10-year follow-up using data from SEER-Medicare. Cancer
Epidemiol Biomarkers Prev. 2012;21:800-809.
5 Sung H, Ferlay J, Siegel RL, et al. Global cancer
statistics 2020: GLOBOCAN estimates of incidence and mortality
worldwide for 36 cancers in 185 countries. CA Cancer J Clin.
2021;71(3):209-249
6 National Cancer Institute, SEER. Cancer Stat Facts:
Female Breast Cancer.
https://seer.cancer.gov/statfacts/html/breast.html. Accessed
September 14, 2021.
Refer
to:
|
Tracy Henrikson;
tracy.henrikson@lilly.com; 609-454-7116 (Lilly): media
|
|
Kevin Hern;
hern_kevin_r@lilly.com; 317-277-1838 (Lilly): investors
|
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