Results from MONARCH 3 show a numerical
improvement in overall survival (OS) of 13.1 months for women with
HR+, HER2- metastatic breast cancer treated with Verzenio plus an
aromatase inhibitor in the intent-to-treat population and 14.9
months for women with visceral disease, however OS outcomes were
not statistically significant
Additional analyses of Verzenio in metastatic
and early breast cancer, as well as imlunestrant (oral SERD) in
combination with Verzenio, will be presented at the meeting
INDIANAPOLIS, Dec. 5, 2023
/PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced
results from the MONARCH 3 clinical trial, which will be presented
in a late-breaking presentation during the 2023 San Antonio Breast
Cancer Symposium (SABCS). MONARCH 3 evaluated
Verzenio® (abemaciclib) in combination with an aromatase
inhibitor (AI) compared to an AI alone as initial endocrine-based
therapy for post-menopausal patients with hormone receptor positive
(HR+), human epidermal growth factor receptor 2 negative (HER2-)
advanced or metastatic breast cancer. At eight years of
follow-up, MONARCH 3 showed women taking Verzenio and an AI had a
median overall survival (OS) of more than 5.5 years – an increase
of 13.1 months compared to the control arm in the intent-to-treat
(ITT) population (66.8 vs 53.7 months), although statistical
significance for the OS outcome was not reached (HR, 0.804; 95% CI,
0.637-1.015; p=0.0664).
For women with visceral organ metastases, data showed a median
OS of more than five years, with an increase in median OS of 14.9
months in the Verzenio arm compared to the control arm (63.7 vs
48.8 months). This included those women whose breast cancer has
spread to the liver or lungs. Patients with visceral disease are at
an increased risk of disease progression and death compared to
metastatic breast cancer (MBC) patients without visceral
metastases. The OS results for this subpopulation were also not
statistically significant (HR, 0.758; 95% CI, 0.558-1.030;
p=0.0757).
"At eight years of follow-up, when the natural history of
metastatic breast cancer starts to substantially impact patient
survival, it is highly encouraging to see abemaciclib combined with
AI therapy deliver a meaningful survival difference of 13 months in
the ITT population and more than 14 months in women at even higher
risk due to visceral disease," said Stephen
Johnston M.D., Ph.D., Professor of Breast Cancer Medicine
and Consultant Medical Oncologist at The Royal Marsden NHS
Foundation Trust (London, U.K.)
and investigator on the MONARCH 3 trial. "Despite missing
statistical significance, these data are clinically relevant and
highly consistent with the overall body of evidence for abemaciclib
in advanced or metastatic breast cancer."
The median progression free survival (PFS) benefit, the primary
endpoint of the MONARCH 3 study, was maintained (29.0 vs 14.8
months; HR, 0.535; 95% CI, 0.429-0.668; nominal p<0.0001), with
substantial difference in 6-year PFS rates (23.3% in the Verzenio
arm vs 4.3% in the control arm). PFS statistical significance was
achieved in an interim analysis in 2017, leading to global
regulatory approvals for this indication in 2018. No new
safety signals were observed with longer-term use.
"With a median OS of more than 5.5 years in patients treated
with Verzenio in this study, these data further support the role of
Verzenio in the survival of women with HR+, HER2- metastatic breast
cancer," said David Hyman, M.D.,
chief medical officer, Lilly. "We remain confident in the
differentiated profile of Verzenio and we look forward to sharing
these results with the clinical community at SABCS and getting
their perspective on these data and relevance for clinical
practice."
The full results will be shared in a late-breaking
presentation on Wednesday, December
6, 11:45 a.m. – 12:00 p.m. CST in General Session 1, Hall
1.
Additional Verzenio data will be presented at SABCS. In early
breast cancer (EBC), an oral presentation will provide results from
genomic and transcriptomic profiling analyses of archived primary
tumor tissue from patients with HR+, HER2-, node-positive, high
risk EBC in the monarchE trial and associate it with the study's
ITT clinical outcomes. A poster spotlight discussion will show
results from a pilot study exploring ctDNA detection using a
tumor-informed assay in the monarchE trial to identify patients at
high risk of recurrence. Other planned Verzenio disclosures in both
MBC and EBC are listed in the table below.
Imlunestrant (investigational oral SERD)
Updated
results from the EMBER study of imlunestrant monotherapy as well as
imlunestrant in combination with Verzenio, with or without an AI,
in patients with estrogen receptor positive (ER+), HER2- advanced
breast cancer will be presented in a spotlight poster
discussion. With 5.5 months longer follow-up from the last
disclosure, imlunestrant plus Verzenio with or without an AI
resulted in an ORR of 62% and 32%, respectively, and a clinical
benefit rate (CBR) of 79% and 71%, respectively. CBR is the
percentage of patients with advanced or metastatic cancer who have
achieved complete response, partial response and prolonged stable
disease for 24 weeks or more. The most common TEAEs for patients
treated with imlunestrant plus Verzenio were diarrhea, nausea,
fatigue, and neutropenia. No safety signals related to ocular or
cardiac toxicity were observed. Side effects from imlunestrant were
generally low grade and there were few dose reductions or
discontinuations of imlunestrant.
A full list of abstract titles and viewing details are listed
below:
Medicine
|
Abstract
Title
|
Presentation
Details
|
Verzenio
(abemaciclib)
|
MONARCH 3: Final
overall survival results of abemaciclib plus a nonsteroidal
aromatase inhibitor as first-line therapy in patients with HR+,
HER2- advanced breast cancer
|
Abstract #:
1643629
Presentation ID:
GS01-12
Session Type:
Late Breaking Oral
Date & Time:
Wednesday, December 6, 11:45 a.m. – 12:00 p.m. CST
Presenter: M
Goetz
|
Verzenio
(abemaciclib)
|
Genomic and
transcriptomic profiling of primary tumors from patients with HR+,
HER2-, node-positive, high-risk early breast cancer in the monarchE
trial
|
Abstract #:
1569529
Poster ID:
GS03-06
Session Type:
Oral
Date & Time:
Friday, December 8, 9:35 – 9:45 a.m. CST
Presenter: N
Turner
|
Verzenio
(abemaciclib)
|
Results from a pilot
study exploring ctDNA detection using a tumor-informed assay in the
monarchE trial of adjuvant abemaciclib with endocrine therapy in
HR+, HER2-, node-positive, high-risk early breast cancer
|
Abstract #:
1580352
Poster ID:
PS06-01
Session Type:
Poster Spotlight Discussion
Date & Time:
Wednesday, December 6, 7:00 – 7:04 a.m. CST
Presenter: S
Graff
|
Verzenio
(abemaciclib)
|
Safety profiles of
Chinese breast cancer patients who received abemaciclib in MONARCH
plus and monarchE study
|
Abstract #:
1575371
Poster ID:
PO1-13-01
Session Type:
Poster Session 1
Date & Time:
Wednesday, December 6, 12:00 – 2:00 p.m. CST
Presenter: Z
Jiang
|
Verzenio
(abemaciclib)
|
Real-world clinical
outcomes in US patients with brain metastases secondary to
HR+/HER2- metastatic breast cancer treated with
abemaciclib
|
Abstract #:
1577336
Poster ID:
PO1-17-01
Session Type:
Poster Session 1
Date & Time:
Wednesday, December 6, 12:00 – 2:00 p.m. CST
Presenter: W
Mwangi
|
Verzenio
(abemacliclib)
|
Circulating tumor DNA
mutation landscape in HR+/HER2− patients with mBC treated with
cyclin-dependent kinase 4/6 inhibitors in the SCRUM-Japan
MONSTAR-SCREEN study
|
Abstract #:
1549969
Poster ID:
PO1-13-02
Session Type:
Poster Session 1
Date & Time:
Wednesday, December 6, 12:00 – 2:00 p.m. CST
Presenter: M
Hattori
|
Imlunestrant
|
Imlunestrant
monotherapy and in combination with abemaciclib, with or without an
aromatase inhibitor, in estrogen receptor-positive (ER+),
HER2-negative (HER2-) advanced breast cancer (aBC): updated results
from the EMBER study
|
Abstract #:
1545518
Poster ID:
PS15-09
Session Type:
Poster Spotlight Discussion
Date & Time:
Thursday, December 7, 6:12 – 6:16 p.m. CST
Presenter: KL
Jhaveri
|
About the MONARCH 3 Study
MONARCH 3 was a Phase
3, double-blind, placebo-controlled study designed to evaluate the
safety and efficacy of Verzenio in combination with an aromatase
inhibitor (AI) (anastrozole or letrozole), as initial
endocrine-based therapy for postmenopausal women with HR+, HER2-
advanced (locoregionally recurrent or metastatic) breast cancer who
have had no prior systemic treatment for advanced disease. If
neoadjuvant/adjuvant endocrine therapy was administered, a
disease-free interval of more than 12 months since completion of
endocrine therapy was required. A total of 493 patients were
randomized 2:1 to receive 150 mg of Verzenio or placebo orally
twice a day, without interruption, given in combination with either
1 mg of anastrozole or 2.5 mg of letrozole once daily until disease
progression or unacceptable toxicity. The primary endpoint of the
study was progression-free survival (PFS) and secondary endpoints
include overall survival (OS), overall response rate (ORR),
duration of response (DoR), and safety. OS is the only
alpha-controlled secondary outcome measure, and this analysis is
split among two populations (intent-to-treat [ITT] and the subgroup
with visceral disease).
About Metastatic Breast Cancer
Advanced breast cancer includes metastatic breast cancer, meaning
cancer that has spread from the breast tissue to other parts of the
body, and locally or regionally advanced breast cancer, meaning the
cancer has grown outside the organ where it started but has not yet
spread to other parts of the body.1 Of all
early-stage breast cancer cases diagnosed in the U.S.,
approximately 30% will become metastatic2 and an
estimated 6-10% of all new breast cancer cases are initially
diagnosed as being metastatic.3 Survival is lower
among women with a more advanced stage of disease at diagnosis:
five-year relative survival is 99% for localized disease, 86% for
regional disease, and 30% for metastatic disease.4
Other factors, such as tumor size, also impact five-year survival
estimates.4
About Breast Cancer
Breast cancer has 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 more than 300,000 new
cases of breast cancer diagnosed in 2023. Breast cancer is the
second leading cause of cancer death in women in the
U.S.6
About Verzenio®
(abemaciclib)
Verzenio® (abemaciclib) is approved
to treat people with certain HR+, HER2- breast cancers in the
adjuvant and advanced or metastatic setting. Verzenio is the first
and only CDK4/6 inhibitor approved to treat node-positive, high
risk early breast cancer (EBC) patients.7 For HR+,
HER2- breast cancer, The National Comprehensive Cancer
Network® (NCCN®) recommends consideration of
two years of abemaciclib (Verzenio) added to endocrine therapy as a
Category 1 treatment option in the adjuvant
setting.8 NCCN® also includes Verzenio
plus endocrine therapy as a preferred treatment option for HR+,
HER2- metastatic breast cancer.8
The collective results of Lilly's clinical development program
continue to differentiate Verzenio as a CDK4/6 inhibitor. In HR+,
HER2-, high risk EBC, Verzenio has shown a persistent and deepening
benefit beyond the two-year treatment period in the monarchE trial,
the only adjuvant study designed to investigate a CDK4/6 inhibitor
specifically in a node-positive, high risk EBC
population.9 In HR+, HER2-, metastatic breast
cancer, Verzenio has demonstrated statistically significant overall
survival in the Phase 3 MONARCH 2 study.10 Verzenio
has shown a consistent and generally manageable safety profile
across clinical trials. In addition to breast cancer, Lilly is
studying Verzenio in different forms of difficult-to-treat prostate
cancer.
Verzenio is an oral tablet taken twice daily and available in
strengths of 50 mg, 100 mg, 150 mg, and 200 mg. Discovered and
developed by Lilly researchers, Verzenio was first approved in 2017
and is currently authorized for use in more than 90 counties around
the world. For full details on indicated uses of Verzenio in HR+,
HER2- breast cancer, please see full Prescribing Information,
available at www.Verzenio.com.
INDICATIONS FOR
VERZENIO®
VERZENIO® is a kinase
inhibitor indicated:
- in combination with endocrine therapy (tamoxifen or an
aromatase inhibitor) for the adjuvant treatment of adult patients
with hormone receptor (HR)-positive, human epidermal growth factor
receptor 2 (HER2)-negative, node-positive, early breast cancer at
high risk of recurrence.
- in combination with an aromatase inhibitor as initial
endocrine-based therapy for the treatment of adult patients with
hormone receptor (HR)-positive, human epidermal growth factor
receptor 2 (HER2)-negative advanced or metastatic breast
cancer.
- in combination with fulvestrant for the treatment of adult
patients with hormone receptor (HR)-positive, human epidermal
growth factor receptor 2 (HER2)-negative advanced or metastatic
breast cancer with disease progression following endocrine
therapy.
- as monotherapy for the treatment of adult patients with
HR-positive, HER2-negative advanced or metastatic breast cancer
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 and Patient
Information for Verzenio.
AL HCP ISI 12OCT2021
About the EMBER Study
This global, first-in-human, open-label Phase 1a/b trial evaluates
imlunestrant alone or in combination with other anticancer
therapies in participants with ER+ advanced breast cancer or
endometrioid endometrial cancer. The trial includes a Phase 1a dose
escalation phase and a Phase 1b dose
expansion phase. The Phase 1a dose escalation enrolls patients with
ER+, HER2- advanced breast cancer who have received up to three
prior treatment regimens and ER+ EEC who have progressed after
prior platinum-based therapy. The dose escalation phase followed an
i3+3 design with imlunestrant administered orally in 28-day cycles.
As dose cohorts were cleared, additional patient enrollment to
cleared dose levels was permitted. The primary objective of the
Phase 1a portion is to determine the recommended Phase 2 dose.
Secondary objectives include assessments of safety,
pharmacokinetics, and anti-tumor activity (objective response rate
[ORR] and clinical benefit rate [CBR], as assessed per Response
Evaluation Criteria in Solid Tumors [RECIST v1.1]).
About Imlunestrant
Imlunestrant (LY3484356) is an
investigational, next-generation oral selective estrogen receptor
degrader (SERD) with pure antagonistic properties. The estrogen
receptor (ER) is the key therapeutic target for patients with
ER+/HER2- breast cancer. Novel degraders of ER may overcome
endocrine therapy resistance while providing consistent oral
pharmacology and convenience of administration. Imlunestrant was
specifically designed to deliver continuous estrogen receptor
target inhibition throughout the dosing period and regardless of
ESR1 mutational status. Imlunestrant is currently being studied in
several clinical studies.
About Lilly
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innovative clinical trials that reflect the diversity of our world
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Verzenio® is a registered trademark owned or licensed
by Eli Lilly and Company, its subsidiaries, or affiliates.
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.
©Lilly USA, LLC 2023. ALL
RIGHTS RESERVED.
Cautionary Statement Regarding Forward-Looking
Statements
This press release contains forward-looking
statements (as that term is defined in the Private Securities
Litigation Reform Act of 1995) about Verzenio as a treatment for
people with certain types of breast cancer and imlunestrant as a
potential treatment for people with certain types of 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 drug research, development, and
commercialization. Among other things, there is no guarantee that
planned or ongoing studies will be completed as planned, that
future study results will be consistent with study results to date,
that Verzenio will receive additional regulatory approvals, or that
imlunestrant will prove to be a safe and effective treatment for
certain types of breast cancer or receive regulatory approval. For
further discussion of these and other risks and uncertainties that
could cause actual results to differ from Lilly's expectations, see
Lilly's 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 American Cancer Society. Understanding Advanced
Cancer, Metastatic Cancer and Bone Metastases.
https://www.cancer.org/treatment/understanding-your-diagnosis/advanced-cancer/what-is.html.
Accessed November 30, 2023.
2 O'Shaughnessy J. Extending survival with chemotherapy
in metastatic breast cancer. Oncologist. 2005;10 Suppl
3:20-9. PMID: 16368868 DOI: 10.1634/theoncologist.10-90003-20.
3 Metastatic Breast Cancer Network. 13 Facts about
Metastatic Breast Cancer.
http://www.mbcn.org/13-facts-about-metastatic-breast-cancer/.
Accessed November 30, 2023.
4 American Cancer Society. Breast Cancer Facts &
Figures 2022-2024. Atlanta:
American Cancer Society, Inc. 2022.
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/2022-2024-breast-cancer-fact-figures-acs.pdf.
Accessed November 30, 2023.
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 American Cancer Society. Cancer Statistics Center.
http://cancerstatisticscenter.cancer.org. Accessed November 30, 2023.
7 Verzenio. Prescribing information. Lilly USA, LLC.
8 Referenced with permission from the NCCN Clinical
Practice Guidelines in Oncology (NCCN Guidelines®) for
Breast Cancer V.4.2023. © National Comprehensive Cancer Network,
Inc. 2023. All rights reserved. Accessed October 18, 2023. To view the most recent and
complete version of the guidelines, go online to NCCN.org. 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.
9 Johnston SRD, Toi M, O'Shaughnessy J, Rastogi P, et
al. Abemaciclib plus endocrine therapy for hormone
receptor-positive, HER2-negative, node-positive, high-risk early
breast cancer (monarchE): results from a preplanned interim
analysis of a randomised, open-label, phase 3 trial. Lancet
Oncol. 2023 Jan;24(1):77-90.
10 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. JAMA
Oncol. 2020;6(1):116-124. doi:10.1001/jamaoncol. 2019.4782.
Refer to: Tracy Henrikson; tracy.henrikson@lilly.com;
(609) 454-7116 – media
Joe Fletcher; jfletcher@lilly.com; (317) 296-2884 –
investors
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