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Bayer
Unveils Latest Data from Oncology Portfolio at ESMO Congress 2023
2023-10-12
·
BioSpace
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Bayer
’s focus remains on
prostate cancer
care with
NUBEQA
® (
darolutamide
), supported by additional ARASENS and ARAMIS trial analyses, evaluating prostate-specific antigen (PSA) outcomes in
metastatic hormone-sensitive prostate cancer (mHSPC)
, and health-related quality of life (HRQoL) deterioration-free survival (DetFS) in patients with
non-metastatic castration-resistant prostate cancer (nmCRPC)
New data from the REASSURE observational study of Xofigo® (radium Ra 223 dichloride) will explore clinical outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) Real-world data will explore Stivarga® (regorafenib) in refractory metastatic colorectal cancer (mCRC), in addition to the safety and effectiveness in unresectable hepatocellular carcinoma (uHCC)
Bayer
will present data from a post-hoc pooled analysis of three clinical trials evaluating
Vitrakvi
® (
larotrectinib
) in the treatment of patients with treatment-naïve
non-primary central nervous system (CNS)
TRK fusion cancer, alongside updated efficacy and safety data from three pooled clinical trials evaluating
Vitrakvi
for the treatment of patients with TRK fusion cancer
Bayer
will highlight the first disclosure of investigational clinical data from a first-in-human, Phase I trial of
BAY 2927088
, an oral tyrosine kinase inhibitor (TKI) in patients with
EGFR
or
HER2
mutant non-small cell lung cancer (NSCLC) Presentations: 1784P, 1781P, 1816P, 616P, 994P, 667P, 668P, 1320MO WHIPPANY, N.J.--(BUSINESS WIRE)--
Bayer
will present new data from across its oncology portfolio at the upcoming European Society for Medical Oncology (ESMO) Congress taking place in Madrid, Spain from October 20-24, 2023. The breadth of new data showcases
Bayer
’s ongoing commitment to supporting patients living with
cancer
.
NUBEQA
® (
darolutamide
) data includes further analyses from the Phase III ARASENS trial which evaluates prostate-specific antigen (PSA) outcomes of
NUBEQA
plus androgen deprivation therapy (ADT) and
docetaxel
, compared to ADT and
docetaxel
by disease volume in
metastatic hormone-sensitive prostate cancer (mHSPC)
. In addition,
Bayer
will present new data on health-related quality of life (HRQoL) deterioration-free survival (DetFS) by
PSA
decline in the Phase III ARAMIS trial in patients with
non-metastatic castration-resistant prostate cancer (nmCRPC)
.
NUBEQA
is currently indicated in the U.S. in combination with
docetaxel
for the treatment of adult patients with
mHSPC
and for the treatment of adult patients with nmCRPC.1
Bayer
will also present new data from the REASSURE observational study, evaluating the clinical outcomes of patients with
metastatic castration-resistant prostate cancer (mCRPC)
who received combined treatment with
Xofigo
® (
radium Ra 223 dichloride
) and
enzalutamide
.
Xofigo
is indicated for the treatment of patients with
mCRPC
,
symptomatic bone metastases
, and no known
visceral metastatic disease.2
Bayer
remains committed to
gastrointestinal (GI) cancer
care. New real-world data featuring
Stivarga
® (
regorafenib
) explores the clinical outcomes of
Stivarga
-treated patients when administered prior to
trifluridine
/
tipiracil
±
bevacizumab
in patients with
refractory metastatic colorectal cancer (mCRC)
. Additionally,
Bayer
will highlight data from the REFINE study, evaluating the safety and effectiveness of
Stivarga
in patients with
unresectable hepatocellular carcinoma (uHCC)
and prior liver transplantation (PLT).
Stivarga
is indicated for the treatment of patients with
mCRC
who have been previously treated with
fluoropyrimidine
-
oxaliplatin
- and
irinotecan
-based chemotherapy, an anti-
VEGF
therapy, and, if
RAS
wild-type, an anti-
EGFR
therapy.
Stivarga
is indicated for the treatment of patients with
hepatocellular carcinoma (HCC)
who have been previously treated with sorafenib.3
Bayer
will highlight the latest efficacy and safety data of
Vitrakvi
® (
larotrectinib
), including data from a post-hoc pooled analysis of three clinical trials evaluating
Vitrakvi
in the treatment of patients with treatment-naïve
non-primary central nervous system (CNS) TRK fusion cancer
, and updated data from a pooled analysis from three clinical trials of patients with longer follow-up.
Vitrakvi
is approved for the treatment of adult and pediatric patients with
solid tumors
that have a
NTRK
gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. Patients should be selected for therapy based on a FDA-approved test. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.4
Bayer
will highlight the latest data from its precision oncology pipeline, including the first disclosure of investigational clinical data from a first-in-human, Phase I trial of
BAY 2927088
, an oral tyrosine kinase inhibitor (TKI) in patients with
non-small cell lung cancer (NSCLC)
. Details on presentations from
Bayer
for the 2023 ESMO Congress are listed below:
Darolutamide
Prostate-specific antigen (PSA) outcomes with
darolutamide
(DARO), androgen-deprivation therapy (ADT) and
docetaxel
(DOC) in patients (pts) with high- and low-
volume metastatic hormone-sensitive prostate cancer (mHSPC)
in ARASENS E-Poster: 1784P; October 22 Health-related quality of life (HRQoL) deterioration-free survival (DetFS) by
prostate-specific antigen (PSA)
decline in
darolutamide (DARO)-treated
patients with
nonmetastatic castration-resistant prostate cancer (nmCRPC)
from ARAMIS E-Poster: 1781P; October 22
Radium-223 dichloride (Ra-223)
Combination treatment with
radium-223 (223Ra)
and
enzalutamide (enza)
in patients (pts) with
metastatic castration-resistant prostate cancer (mCRPC)
in the REASSURE study E-Poster: 1816P; October 22
Regorafenib
Sequential treatment with
regorafenib
(REG) and
trifluridine
/
tipiracil
(TAS) +/- bevacizumab (Bev) in
refractory metastatic colorectal cancer (mCRC)
in community clinical practice in the USA E-Poster: 616P; October 22
Regorafenib
(REG) in patients (pts) with
unresectable hepatocellular carcinoma (uHCC)
in real-world (RW) practice: Final analysis of the prospective, observational REFINE study by prior liver transplantation (PLT) E-Poster: 994P; October 23
Larotrectinib
Efficacy and safety of
larotrectinib (laro)
as first-line treatment for patients (pts) with tropomyosin receptor kinase (TRK) fusion cancer E-Poster: 667P; October 23 Efficacy and Safety of
Larotrectinib
in a Pooled Analysis of Patients (Pts) with Tropomyosin Receptor Kinase (TRK) Fusion Cancer E-Poster: 668P; October 23 Precision Oncology Pipeline Early evidence of efficacy in patients (pts) with
non-small cell lung cancer (NSCLC)
with
HER2
exon20 insertion (ex20ins) mutations treated in a Phase I study with
BAY 2927088
Oral Presentation: 1320MO; October 23 About
NUBEQA
® (
darolutamide)1
NUBEQA
is an
androgen receptor inhibitor (ARi)
with a distinct chemical structure that competitively inhibits androgen binding,
AR
nuclear translocation, and
AR
-mediated transcription. On July 30, 2019, the FDA approved
NUBEQA
® (
darolutamide
) based on the ARAMIS trial, a randomized, double-blind, placebo-controlled, multi-center Phase III study, which evaluated the safety and efficacy of oral
NUBEQA
in patients with
non-metastatic castration-resistant prostate cancer (nmCRPC)
. Based on results from the ARASENS trial, a randomized, Phase III, multi-center, double-blind, placebo-controlled trial,
NUBEQA
plus androgen deprivation therapy (ADT) and
docetaxel
was approved on August 5, 2022 for the treatment of adult patients with
metastatic hormone-sensitive prostate cancer (mHSPC)
.
NUBEQA
is also being investigated in additional studies across various stages of
prostate cancer
, including in the ARANOTE Phase III trial evaluating
NUBEQA
plus ADT versus ADT alone for
mHSPC
, as well as in the Australian and New Zealand
Urogenital and Prostate Cancer
Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating
NUBEQA
as an adjuvant treatment for
localized prostate cancer
with very high risk of recurrence. Information about these trials can be found at Developed jointly by
Bayer
and
Orion Corporation
, a globally operating Finnish pharmaceutical company,
NUBEQA
is indicated for the treatment of adults with nmCRPC or with mHSPC in combination with docetaxel.1 Filings in other regions are underway or planned. INDICATIONS
NUBEQA
® (
darolutamide
) is an
androgen receptor
inhibitor indicated for the treatment of adult patients with:
Non-metastatic castration-resistant prostate cancer (nmCRPC)
Metastatic hormone-sensitive prostate cancer (mHSPC)
in combination with
docetaxel
IMPORTANT SAFETY INFORMATION Warnings & Precautions
Ischemic Heart Disease
– In a study of patients with nmCRPC (ARAMIS),
ischemic heart disease
occurred in 3.2% of patients receiving
NUBEQA
versus 2.5% receiving placebo, including Grade 3-4 events in 1.7% vs. 0.4%, respectively. Ischemic events led to death in 0.3% of patients receiving
NUBEQA
vs. 0.2% receiving placebo. In a study of patients with mHSPC (ARASENS),
ischemic heart disease
occurred in 2.9% of patients receiving
NUBEQA
with
docetaxel
vs. 2% receiving placebo with
docetaxel
, including Grade 3-4 events in 1.3% vs. 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving
NUBEQA
with
docetaxel
vs. 0% receiving placebo with
docetaxel
. Monitor for signs and symptoms of
ischemic heart disease
. Optimize management of cardiovascular risk factors, such as
hypertension
,
diabetes
, or
dyslipidemia
. Discontinue
NUBEQA
for Grade 3-4
ischemic heart disease
. Seizure – In ARAMIS, Grade 1-2 seizure occurred in 0.2% of patients receiving
NUBEQA
vs. 0.2% receiving placebo. Seizure occurred 261 and 456 days after initiation of
NUBEQA
. In ARASENS,
seizure
occurred in 0.6% of patients receiving
NUBEQA
with
docetaxel
, including one Grade 3 event, vs. 0.2% receiving placebo with
docetaxel
. Seizure occurred 38 to 340 days after initiation of
NUBEQA
. It is unknown whether anti-
epileptic
medications will prevent
seizures
with
NUBEQA
. Advise patients of the risk of developing a
seizure
while receiving
NUBEQA
and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others. Consider discontinuation of
NUBEQA
in patients who develop a
seizure
during treatment. Embryo-Fetal Toxicity – Safety and efficacy of
NUBEQA
have not been established in females.
NUBEQA
can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with
NUBEQA
and for 1 week after the last dose. Adverse Reactions In ARAMIS, serious adverse reactions occurred in 25% of patients receiving
NUBEQA
vs. 20% of patients receiving placebo. Serious adverse reactions in ≥1% of patients who received
NUBEQA
included
urinary retention
,
pneumonia
, and
hematuria
. Fatal adverse reactions occurred in 3.9% of patients receiving
NUBEQA
vs. 3.2% of patients receiving placebo. Fatal adverse reactions in patients who received
NUBEQA
included death (0.4%),
cardiac failure
(0.3%),
cardiac arrest
(0.2%), general physical health deterioration (0.2%), and
pulmonary embolism
(0.2%). The most common adverse reactions (>2% with a ≥2% increase over placebo), including laboratory test abnormalities, were increased
AST
, decreased neutrophil count,
fatigue
, increased bilirubin,
pain
in extremity, and
rash
. Clinically relevant adverse reactions occurring in ≥2% of patients treated with
NUBEQA
included
ischemic heart disease
and
heart failure
. In ARASENS, serious adverse reactions occurred in 45% of patients receiving
NUBEQA
with
docetaxel
vs. 42% of patients receiving placebo with
docetaxel
. Serious adverse reactions in ≥2% of patients who received
NUBEQA
with
docetaxel
included
febrile neutropenia
(6%), decreased neutrophil count (2.8%),
musculoskeletal pain
(2.6%), and
pneumonia
(2.6%). Fatal adverse reactions occurred in 4% of patients receiving
NUBEQA
with
docetaxel
vs. 4% of patients receiving placebo with
docetaxel
. Fatal adverse reactions in patients who received
NUBEQA
included
COVID-19/COVID-19 pneumonia
(0.8%),
myocardial infarction
(0.3%), and sudden death (0.3%). The most common adverse reactions (≥10% with a ≥2% increase over placebo with
docetaxel
) were
constipation
,
decreased appetite
,
rash
,
hemorrhage
, increased weight, and
hypertension
. The most common laboratory test abnormalities (≥30%) were
anemia
,
hyperglycemia
, decreased lymphocyte count, decreased neutrophil count, increased
AST
, increased ALT, and
hypocalcemia
. Clinically relevant adverse reactions in <10% of patients who received
NUBEQA
with
docetaxel
included
fractures
,
ischemic heart disease
,
seizures
, and
drug-induced liver injury
. Drug Interactions Effect of Other Drugs on
NUBEQA
– Combined
P-gp
and strong or moderate
CYP3A4
inducers
decrease
NUBEQA
exposure, which may decrease
NUBEQA
activity. Avoid concomitant use. Combined
P-gp
and strong
CYP3A4 inhibitors
CYP3A4
inhibitors increase
NUBEQA
exposure, which may increase the risk of
NUBEQA
adverse reactions. Monitor more frequently and modify
NUBEQA
dose as needed. Effects of
NUBEQA
on Other Drugs –
NUBEQA
inhibits breast cancer resistance protein (BCRP) transporter. Concomitant use increases exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of
BCRP
substrate-related toxicities. Avoid concomitant use where possible. If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate.
NUBEQA
inhibits OATP1B1 and OATP1B3 transporters. Concomitant use may increase plasma concentrations of
OATP1B1
or
OATP1B3
substrates. Monitor more frequently for adverse reactions and consider dose reduction of these substrates. Review the Prescribing Information of drugs that are
BCRP
,
OATP1B1
, and
OATP1B3
substrates when used concomitantly with
NUBEQA
. For important risk and use information about
NUBEQA
, please see the accompanying full Prescribing Information. About
Xofigo
® (
radium Ra 223 dichloride
) Injection2
Xofigo
is indicated for the treatment of patients with
castration-resistant prostate cancer
, symptomatic
bone metastases
and no known
visceral metastatic disease
. Important Safety Information for
Xofigo
® (radium Ra 223 dichloride) Injection Warnings and Precautions: Bone Marrow Suppression: In the phase 3 ALSYMPCA trial, 2% of patients in the
Xofigo
arm experienced
bone marrow failure
or ongoing
pancytopenia
, compared to no patients treated with placebo. There were two deaths due to
bone marrow failure
. For 7 of 13 patients treated with
Xofigo
bone marrow failure
was ongoing at the time of death. Among the 13 patients who experienced
bone marrow failure
, 54% required blood transfusions. Four percent (4%) of patients in the
Xofigo
arm and 2% in the placebo arm permanently discontinued therapy due to bone marrow suppression. In the randomized trial, deaths related to
vascular hemorrhage
in association with
myelosuppression
were observed in 1% of
Xofigo
-treated patients compared to 0.3% of patients treated with placebo. The incidence of
infection
-related deaths (2%), serious
infections
(10%), and
febrile neutropenia
(<1%) was similar for patients treated with
Xofigo
and placebo. Myelosuppression–notably
thrombocytopenia
,
neutropenia
,
pancytopenia
, and
leukopenia
–has been reported in patients treated with
Xofigo
. Monitor patients with evidence of compromised bone marrow reserve closely and provide supportive care measures when clinically indicated. Discontinue
Xofigo
in patients who experience life-threatening complications despite supportive care for
bone marrow failure
Hematological Evaluation: Monitor blood counts at baseline and prior to every dose of
Xofigo
. Prior to first administering
Xofigo
, the absolute neutrophil count (ANC) should be ≥1.5 × 109/L, the platelet count ≥100 × 109/L, and hemoglobin ≥10 g/dL. Prior to subsequent administrations, the ANC should be ≥1 × 109/L and the platelet count ≥50 × 109/L. Discontinue
Xofigo
if hematologic values do not recover within 6 to 8 weeks after the last administration despite receiving supportive care Concomitant Use With Chemotherapy: Safety and efficacy of concomitant chemotherapy with
Xofigo
have not been established. Outside of a clinical trial, concomitant use of
Xofigo
in patients on chemotherapy is not recommended due to the potential for additive
myelosuppression
. If chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy are administered during the treatment period,
Xofigo
should be discontinued Increased
Fractures
and Mortality in Combination With
Abiraterone
Plus
Prednisone
/
Prednisolone
:
Xofigo
is not recommended for use in combination with
abiraterone acetate
plus
prednisone
/
prednisolone
outside of clinical trials. At the primary analysis of the Phase 3 ERA-223 study that evaluated concurrent initiation of
Xofigo
in combination with
abiraterone acetate
plus
prednisone
/
prednisolone
in 806 asymptomatic or mildly symptomatic
mCRPC
patients, an increased incidence of
fractures
(28.6% vs 11.4%) and deaths (38.5% vs 35.5%) have been observed in patients who received
Xofigo
in combination with
abiraterone acetate
plus
prednisone
/
prednisolone
compared to patients who received placebo in combination with
abiraterone acetate
plus
prednisone
/
prednisolone
. Safety and efficacy with the combination of
Xofigo
and agents other than
gonadotropin-releasing hormone analogues
have not been established Embryo-Fetal Toxicity: The safety and efficacy of
Xofigo
have not been established in females.
Xofigo
can cause fetal harm when administered to a pregnant female. Advise pregnant females and females of reproductive potential of the potential risk to a fetus. Advise male patients to use condoms and their female partners of reproductive potential to use effective contraception during and for 6 months after completing treatment with
Xofigo
Administration and Radiation Protection:
Xofigo
should be received, used, and administered only by authorized persons in designated clinical settings. The administration of
Xofigo
is associated with potential risks to other persons from radiation or contamination from spills of bodily fluids such as urine, feces, or vomit. Therefore, radiation protection precautions must be taken in accordance with national and local regulations Fluid Status:
Dehydration
occurred in 3% of patients on
Xofigo
and 1% of patients on placebo.
Xofigo
increases adverse reactions such as
diarrhea
,
nausea
, and
vomiting
, which may result in
dehydration
. Monitor patients’ oral intake and fluid status carefully and promptly treat patients who display signs or symptoms of
dehydration
or
hypovolemia
Injection Site Reactions:
Erythema
,
pain
, and
edema
at the injection site were reported in 1% of patients on Xofigo
Secondary Malignant Neoplasms
:
Xofigo
contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure may be associated with an increased risk of
cancer
and hereditary defects. Due to its mechanism of action and neoplastic changes, including
osteosarcomas
, in rats following administration of
radium-223 dichloride
,
Xofigo
may increase the risk of
osteosarcoma
or other
secondary malignant neoplasms
. However, the overall incidence of new
malignancies
in the randomized trial was lower on the
Xofigo
arm compared to placebo (<1% vs 2%; respectively), but the expected latency period for the development of
secondary malignancies
exceeds the duration of follow-up for patients on the trial Subsequent Treatment With Cytotoxic Chemotherapy: In the randomized clinical trial, 16% of patients in the
Xofigo
group and 18% of patients in the placebo group received cytotoxic chemotherapy after completion of study treatments. Adequate safety monitoring and laboratory testing was not performed to assess how patients treated with
Xofigo
will tolerate subsequent cytotoxic chemotherapy Adverse Reactions: The most common adverse reactions (≥10%) in the
Xofigo
arm vs the placebo arm, respectively, were
nausea
(36% vs 35%),
diarrhea
(25% vs 15%),
vomiting
(19% vs 14%), and
peripheral edema
(13% vs 10%). Grade 3 and 4 adverse events were reported in 57% of
Xofigo
-treated patients and 63% of placebo-treated patients. The most common
hematologic laboratory abnormalities
in the
Xofigo
arm (≥10%) vs the placebo arm, respectively, were
anemia
(93% vs 88%),
lymphocytopenia
(72% vs 53%),
leukopenia
(35% vs 10%),
thrombocytopenia
(31% vs 22%), and
neutropenia
(18% vs 5%) Please see the full Prescribing Information for
Xofigo
(
radium Ra 223 dichloride
). About
Stivarga
®
(regorafenib)3
In April 2017,
Stivarga
was approved for use in patients with
hepatocellular carcinoma
who have been previously treated with
sorafenib
. In the United States,
Stivarga
is also indicated for the treatment of patients with
metastatic colorectal cancer (CRC)
who have been previously treated with
fluoropyrimidine
-,
oxaliplatin
- and
irinotecan
-based chemotherapy, an anti-
VEGF
therapy, and, if
RAS
wild-type, an anti-
EGFR
therapy. It is also indicated for the treatment of patients with
locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST)
who have been previously treated with
imatinib mesylate
and
sunitinib malate
.
Regorafenib
is a compound developed by
Bayer
. In 2011,
Bayer
entered into an agreement with
Onyx
, now an
Amgen
subsidiary, under which
Onyx
receives a royalty on all global net sales of
regorafenib
in oncology. Indication
Stivarga
is indicated for the treatment of patients with
metastatic colorectal cancer (CRC)
who have been previously treated with
fluoropyrimidine
-,
oxaliplatin
- and
irinotecan
-based chemotherapy, an anti-
VEGF
therapy, and, if
RAS
wild- type, an anti-
EGFR
therapy.
Stivarga
is indicated for the treatment of patients with
locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST)
who have been previously treated with
imatinib mesylate
and
sunitinib malate
.
Stivarga
is indicated for the treatment of patients with
hepatocellular carcinoma (HCC)
who have been previously treated with
sorafenib
. Important Safety Information for
STIVARGA
® (
regorafenib
) WARNING: HEPATOTOXICITY Severe and sometimes fatal hepatotoxicity has occurred in clinical trials. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue
STIVARGA
for hepatotoxicity as manifested by elevated liver function tests or
hepatocellular necrosis
, depending upon severity and persistence. Hepatotoxicity: Severe
drug-induced liver injury
with fatal outcome occurred in
STIVARGA
-treated patients across all clinical trials. In most cases, liver dysfunction occurred within the first 2 months of therapy and was characterized by a hepatocellular pattern of injury. In
metastatic colorectal cancer (mCRC)
, fatal
hepatic failure
occurred in 1.6% of patients in the
STIVARGA
arm and in 0.4% of patients in the placebo arm. In
gastrointestinal stromal tumor (GIST)
, fatal
hepatic failure
occurred in 0.8% of patients in the
STIVARGA
arm. In
hepatocellular carcinoma (HCC)
, there was no increase in the incidence of
fatal hepatic failure
as compared to placebo. Liver Function Monitoring: Obtain liver function tests (ALT,
AST
, and bilirubin) before initiation of
STIVARGA
and monitor at least every 2 weeks during the first 2 months of treatment. Thereafter, monitor monthly or more frequently as clinically indicated. Monitor liver function tests weekly in patients experiencing elevated liver function tests until improvement to less than 3 times the upper limit of normal (ULN) or baseline values. Temporarily hold and then reduce or permanently discontinue
STIVARGA
, depending on the severity and persistence of hepatotoxicity as manifested by elevated liver function tests or
hepatocellular necrosis
.
Infections
:
STIVARGA
caused an increased risk of
infections
. The overall incidence of
infection
(Grades 1-5) was higher (32% vs 17%) in 1142
STIVARGA
-treated patients as compared to the control arm in randomized placebo-controlled trials. The incidence of grade 3 or greater
infections
in
STIVARGA
treated patients was 9%. The most common
infections
were
urinary tract infections
(5.7%),
nasopharyngitis
(4.0%),
mucocutaneous and systemic fungal infections
(3.3%) and
pneumonia
(2.6%). Fatal outcomes caused by
infection
occurred more often in patients treated with
STIVARGA
(1.0%) as compared to patients receiving placebo (0.3%); the most common fatal
infections
were respiratory (0.6% vs 0.2%). Withhold
STIVARGA
for Grade 3 or 4 infections, or worsening
infection
of any grade. Resume
STIVARGA
at the same dose following resolution of
infection
.
Hemorrhage
:
STIVARGA
caused an increased incidence of
hemorrhage
. The overall incidence (Grades 1-5) was 18.2% in 1142 patients treated with
STIVARGA
vs 9.5% with placebo in randomized, placebo-controlled trials. The incidence of grade 3 or greater
hemorrhage
in patients treated with
STIVARGA
was 3.0%. The incidence of fatal hemorrhagic events was 0.7%, involving the central nervous system or the respiratory, gastrointestinal, or genitourinary tracts. Permanently discontinue
STIVARGA
in patients with severe or life-threatening
hemorrhage
and monitor INR levels more frequently in patients receiving
warfarin
.
Gastrointestinal Perforation
or Fistula:
Gastrointestinal perforation
occurred in 0.6% of 4518 patients treated with
STIVARGA
across all clinical trials of
STIVARGA
administered as a single agent; this included eight fatal events.
Gastrointestinal fistula
occurred in 0.8% of patients treated with
STIVARGA
and in 0.2% of patients in the placebo arm across randomized, placebo-controlled trials. Permanently discontinue
STIVARGA
in patients who develop gastrointestinal perforation or fistula. Dermatological Toxicity: In randomized, placebo-controlled trials, adverse skin reactions occurred in 71.9% of patients with
STIVARGA
arm and 25.5% of patients in the placebo arm including
hand-foot skin reaction (HFSR)
also known as
palmar-plantar erythrodysesthesia syndrome (PPES)
and severe
rash
, requiring dose modification. In the randomized, placebo-controlled trials, the overall incidence of HFSR was higher in 1142
STIVARGA
-treated patients (53% vs 8%) than in the placebo-treated patients. Most cases of HFSR in
STIVARGA
-treated patients appeared during the first cycle of treatment. The incidences of Grade 3 HFSR (16% vs <1%),
Grade 3 rash
(3% vs <1%), serious adverse reactions of
erythema multiforme
(<0.1% vs 0%), and
Stevens-Johnson syndrome
(<0.1% vs 0%) were higher in
STIVARGA
-treated patients. Across all trials, a higher incidence of HFSR was observed in Asian patients treated with
STIVARGA
(all grades: 72%; Grade 3:18%).
Toxic epidermal necrolysis
occurred in 0.02% of 4518
STIVARGA
-treated patients across all clinical trials of
STIVARGA
administered as a single agent. Withhold
STIVARGA
, reduce the dose, or permanently discontinue depending on the severity and persistence of dermatologic toxicity.
Hypertension
:
Hypertensive
crisis occurred in 0.2% in
STIVARGA
-treated patients and in none of the patients in placebo arm across all randomized, placebo-controlled trials.
STIVARGA
caused an increased incidence of
hypertension
(30% vs 8% in
mCRC
, 59% vs 27% in
GIST
, and 31% vs 6% in
HCC
). The onset of
hypertension
occurred during the first cycle of treatment in most patients who developed
hypertension
(67% in randomized, placebo-controlled trials). Do not initiate
STIVARGA
until blood pressure is adequately controlled. Monitor blood pressure weekly for the first 6 weeks of treatment and then every cycle, or more frequently, as clinically indicated. Temporarily or permanently withhold
STIVARGA
for severe or uncontrolled
hypertension
.
Cardiac Ischemia
and
Infarction
:
STIVARGA
increased the incidence of
myocardial ischemia
and
infarction
(0.9% with
STIVARGA
vs 0.2% with placebo) in randomized placebo-controlled trials. Withhold
STIVARGA
in patients who develop new or
acute cardiac ischemia
or
infarction
and resume only after resolution of acute cardiac ischemic events if the potential benefits outweigh the risks of further
cardiac ischemia
.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
:
Reversible posterior leukoencephalopathy syndrome (RPLS)
, a syndrome of
subcortical vasogenic edema
diagnosed by characteristics finding on MRI occurred in one of 4800
STIVARGA
-treated patients across all clinical trials. Perform an evaluation for RPLS in any patient presenting with
seizures
, severe
headache
, visual disturbances,
confusion
, or
altered mental function
. Discontinue
STIVARGA
in patients who develop RPLS. Wound Healing Complications: Impaired wound healing complications can occur in patients who receive drugs that inhibit the
VEGF
signaling pathway. Therefore,
STIVARGA
has the potential to adversely affect wound healing. Withhold
STIVARGA
for at least 2 weeks prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of
STIVARGA
after resolution of wound healing complications has not been established. Embryo-Fetal Toxicity:
STIVARGA
can cause fetal harm when administered to a pregnant woman. There are no available data on
STIVARGA
use in pregnant women. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with
STIVARGA
and for 2 months after the final dose. Nursing Mothers: Because of the potential for serious adverse reactions in breastfed infants from
STIVARGA
, do not breastfeed during treatment with
STIVARGA
and for 2 weeks after the final dose. Most Frequently Observed Adverse Drug Reactions in
mCRC
(≥30%): The most frequently observed adverse drug reactions (≥30%) in
STIVARGA
-treated patients vs placebo-treated patients in
mCRC
, respectively, were:
asthenia
/
fatigue
(64% vs 46%),
pain
(59% vs 48%), decreased appetite and food intake (47% vs 28%), HFSR/PPE (45% vs 7%),
diarrhea
(43% vs 17%),
mucositis
(33% vs 5%),
weight loss
(32% vs 10%),
infection
(31% vs 17%),
hypertension
(30% vs 8%), and dysphonia (30% vs 6%). Most Frequently Observed Adverse Drug Reactions in
GIST
(≥30%): The most frequently observed adverse drug reactions (≥30%) in
STIVARGA
-treated patients vs placebo treated patients in
GIST
, respectively, were: HFSR/PPE (67% vs 12%),
pain
(60% vs 55%),
hypertension
(59% vs 27%),
asthenia
/
fatigue
(52% vs 39%),
diarrhea
(47% vs 9%),
mucositis
(40% vs 8%),
dysphonia
(39% vs 9%),
infection
(32% vs 5%), decreased appetite and food intake (31% vs 21%), and
rash
(30% vs 3%). Most Frequently Observed Adverse Drug Reactions in
HCC
(≥30%): The most frequently observed adverse drug reactions (≥30%) in
STIVARGA
-treated patients vs placebo-treated patients in
HCC
, respectively, were:
pain
(55% vs 44%), HFSR/PPE (51% vs 7%),
asthenia
/
fatigue
(42% vs 33%),
diarrhea
(41% vs 15%),
hypertension
(31% vs 6%),
infection
(31% vs 18%), decreased appetite and food intake (31% vs 15%). Please see full Prescribing Information, including Boxed Warning for Stivarga (regorafenib). About
Vitrakvi
®
(larotrectinib)4
Vitrakvi
® (
larotrectinib
) is indicated for the treatment of adult and pediatric patients with
solid tumors
that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. Select patients for therapy based on an FDA-approved test. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Important Safety Information for
Vitrakvi
® (
larotrectinib
) Warnings and Precautions Central Nervous System Effects: Central nervous system (CNS) adverse reactions occurred in patients receiving
VITRAKVI
, including
dizziness
,
cognitive impairment
,
mood disorders
, and
sleep disturbances
. In patients who received
VITRAKVI
, all grades CNS effects including
cognitive impairment
,
mood disorders
,
dizziness
and
sleep disorders
were observed in 42% with Grades 3-4 in 3.9% of patients.
Cognitive impairment
occurred in 11% of patients. The median time to onset of
cognitive impairment
was 5.6 months (range: 2 days to 41 months).
Cognitive impairment
occurring in ≥ 1% of patients included memory impairment (3.6%),
confusional state
(2.9%),
disturbance in attention
(2.9%),
delirium
(2.2%),
cognitive disorders
(1.4%), and Grade 3 cognitive adverse reactions occurred in 2.5% of patients. Among the 30 patients with
cognitive impairment
, 7% required a dose modification and 20% required dose interruption.
Mood disorders
occurred in 14% of patients. The median time to onset of
mood disorders
was 3.9 months (range: 1 day to 40.5 months).
Mood disorders
occurring in ≥1% of patients included
anxiety
(5%),
depression
(3.9%),
agitation
(2.9%), and
irritability
(2.9%). Grade 3
mood disorders
occurred in 0.4% of patients.
Dizziness
occurred in 27% of patients, and
Grade 3 dizziness
occurred in 1.1% of patients. Among the 74 patients who experienced
dizziness
, 5% of patients required a dose modification and 5% required dose interruption.
Sleep disturbances
occurred in 10% of patients.
Sleep disturbances
included
insomnia
(7%),
somnolence
(2.5%), and
sleep disorder
(0.4%). There were no Grade 3-4
sleep disturbances
. Among the 28 patients who experienced
sleep disturbances
, 1 patient each (3.6%) required a dose modification or dose interruption. Advise patients and caretakers of these risks with
VITRAKVI
. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue
VITRAKVI
based on the severity. If withheld, modify the
VITRAKVI
dosage when resumed.
Skeletal Fractures
: Among 187 adult patients who received
VITRAKVI
across clinical trials,
fractures
were reported in 7% and among 92 pediatric patients,
fractures
were reported in 9% (N=279; 8%). Median time to
fracture
was 11.6 months (range 0.9 to 45.8 months) in patients followed per
fracture
.
Fractures
of the femur, hip or acetabulum were reported in 4 patients (3 adult, 1 pediatric). Most
fractures
were associated with minimal or moderate trauma. Some
fractures
were associated with radiologic abnormalities suggestive of local
tumor
involvement.
VITRAKVI
treatment was interrupted due to
fracture
in 1.4% patients. Promptly evaluate patients with signs or symptoms of potential
fracture
(e.g.,
pain
, changes in mobility,
deformity
). There are no data on the effects of
VITRAKVI
on healing of known
fractures
or risk of future
fractures
. Hepatotoxicity: In patients who received
VITRAKVI
, increased
AST
of any grade occurred in 52% of patients and increased ALT of any grade occurred in 45%. Grade 3-4 increased
AST
or ALT occurred in 3.1% and 2.5% of patients, respectively. The median time to onset of increased
AST
was 2.1 months (range: 1 day to 4.3 years). The median time to onset of increased ALT was 2.3 months (range: 1 day to 4.2 years). Increased
AST
and ALT leading to dose modifications occurred in 1.4% and 2.2% of patients, respectively. Increased
AST
or ALT led to permanent discontinuation in 3 (1.1%) patients. Monitor liver tests, including ALT and
AST
, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue
VITRAKVI
based on the severity. If withheld, modify the
VITRAKVI
dosage when resumed. Embryo-Fetal Toxicity:
VITRAKVI
can cause fetal harm when administered to a pregnant woman.
VITRAKVI
resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of
VITRAKVI
. Adverse Reactions The most common adverse reactions (≥20%), including laboratory abnormalities, were: increased
AST
(52%), increased ALT (45%),
anemia
(42%),
musculoskeletal pain
(42%),
fatigue
(36%),
hypoalbuminemia
(36%),
neutropenia
(36%), increased
alkaline phosphatase
(34%),
cough
(32%),
leukopenia
(28%),
constipation
(27%),
diarrhea
(27%),
dizziness
(27%),
hypocalcemia
(25%),
nausea
(25%),
vomiting
(25%), pyrexia (24%), lymphopenia (22%) and abdominal pain (21%). Drug Interactions Avoid coadministration of
VITRAKVI
with strong
CYP3A4 inhibitors
CYP3A4
inhibitors (including grapefruit or grapefruit juice), strong
CYP3A4
inducers (including St. John’s wort), or sensitive
CYP3A4
substrates. If coadministration of strong
CYP3A4 inhibitors
CYP3A4
inhibitors or inducers cannot be avoided, modify the
VITRAKVI
dose as recommended. If coadministration of sensitive
CYP3A4
substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs. For coadministration with moderate
CYP3A4 inhibitors
CYP3A4
inhibitors, monitor for adverse reactions more frequently and reduce the dosage based on severity. For coadministration with moderate
CYP3A4
inducers, modify dose as recommended. Use in Specific Populations Lactation: Advise women not to breastfeed during treatment with
VITRAKVI
and for 1 week after the final dose. Please see the full Prescribing Information for
VITRAKVI
® (
larotrectinib
). About Oncology at
Bayer
Bayer
is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at
Bayer
includes six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that
cancer
is treated. About
Bayer
Bayer
is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population.
Bayer
is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The
Bayer
brand stands for trust, reliability and quality throughout the world. In fiscal 2022, the Group employed around 101,000 people and had sales of 50.7 billion euros. R&D expenses before special items amounted to 6.2 billion euros. For more information, go to . © 2023
Bayer
BAYER
, the
Bayer Cross
,
NUBEQA
,
Xofigo
,
Stivarga
and
Vitrakvi
are registered trademarks of
Bayer
. Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by
Bayer
management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in
Bayer
’s public reports which are available on the
Bayer
website at . The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. References
NUBEQA
® (
darolutamide
) tablets [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, August 2022.
Xofigo
® (
radium-223 dichloride
) Injection [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, December 2019.
Stivarga
® (
regorafenib
) tablets [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, December 2020.
Vitrakvi
® [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; March 2021. PP-PF-ONC-US-2991-1 10/23
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机构
Bayer AG
Orion Corp
Onyx Inc.
[+1]
适应症
NTRK融合基因阳性的中枢神经系统肿瘤
出血
第二原发肿瘤
[+94]
靶点
EGFR
HER2
KLK3
[+12]
药物
达罗他胺
硫酸拉罗替尼
Sevabertinib
[+19]
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