Fulvestrant (Page 2 of 7)

3 DOSAGE FORMS AND STRENGTHS

Fulvestrant, an injection for intramuscular administration, is supplied as 5-mL single-dose prefilled syringes containing 250 mg/5 mL fulvestrant.

4 CONTRAINDICATIONS

Fulvestrant is contraindicated in patients with a known hypersensitivity to the drug or to any of its components. Hypersensitivity reactions, including urticaria and angioedema, have been reported in association with fulvestrant [seeAdverse Reactions (6.2) ].

5 WARNINGS AND PRECAUTIONS

5.1 Risk of Bleeding

Because fulvestrant is administered intramuscularly, it should be used with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use.

5.2 Increased Exposure in Patients with Hepatic Impairment

The safety and pharmacokinetics of fulvestrant were evaluated in a study in seven subjects with moderate hepatic impairment (Child-Pugh class B) and seven subjects with normal hepatic function. Exposure was increased in patients with moderate hepatic impairment, therefore a dose of 250 mg is recommended [see Dosage and Administration (2.2)].

Fulvestrant has not been studied in patients with severe hepatic impairment (Child-Pugh class C) [see Use in Specific Populations (8.6)].

5.3 Injection Site Reaction

Injection site related events including sciatica, neuralgia, neuropathic pain, and peripheral neuropathy have been reported with fulvestrant injection. Caution should be taken while administering fulvestrant at the dorsogluteal injection site due to the proximity of the underlying sciatic nerve [seeDosage and Administration (2.3) and Adverse Reactions (6.1)].

5.4 Embryo-Fetal Toxicity

Based on findings from animal studies and its mechanism of action, fulvestrant can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of fulvestrant to pregnant rats and rabbits during organogenesis resulted in embryo-fetal toxicity at daily doses that are significantly less than 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 fulvestrant and for one year after the last dose [seeUse in Specific Populations(8.1), (8.3) and Clinical Pharmacology (12.1)].

5.5 Immunoassay Measurement of Serum Estradiol

Due to structural similarity of fulvestrant and estradiol, fulvestrant can interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels.

6 ADVERSE REACTIONS

The following adverse reactions are discussed in more detail in other sections of the labeling:

Risk of Bleeding [see Warnings and Precautions (5.1)]
Increased Exposure in Patients with Hepatic Impairment [see Warnings and Precautions (5.2)]
Injection Site Reaction [see Warnings and Precautions (5.3)]
Embryo-Fetal Toxicity [see Warnings and Precautions (5.4)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice.

Monotherapy

Comparison of Fulvestrant 500 mg and Fulvestrant 250 mg (CONFIRM)

The following adverse reactions (ARs) were calculated based on the safety analysis of CONFIRM comparing the administration of fulvestrant 500 mg intramuscularly once a month with fulvestrant 250 mg intramuscularly once a month. The most frequently reported adverse reactions in the fulvestrant 500 mg group were injection site pain (11.6% of patients), nausea (9.7% of patients) and bone pain (9.4% of patients); the most frequently reported adverse reactions in the fulvestrant 250 mg group were nausea (13.6% of patients), back pain (10.7% of patients) and injection site pain (9.1% of patients).

Table 1 lists adverse reactions reported with an incidence of 5% or greater, regardless of assessed causality, from CONFIRM.

Table 1: Adverse Reactions in CONFIRM (≥5% in Either Treatment Group)

*
Including more severe injection site related sciatica, neuralgia, neuropathic pain, and peripheral neuropathy.

Adverse Reactions

Fulvestrant 500 mg

N=361

%

Fulvestrant 250 mg

N=374

%

Body as a Whole

Injection Site Pain *

12

9

Headache

8

7

Back Pain

8

11

Fatigue

8

6

Pain in Extremity

7

7

Asthenia

6

6

Vascular System

Hot Flash

7

6

Digestive System

Nausea

10

14

Vomiting

6

6

Anorexia

6

4

Constipation

5

4

Musculoskeletal System

Bone Pain

9

8

Arthralgia

8

8

Musculoskeletal Pain

6

3

Respiratory System

Cough

5

5

Dyspnea

4

5

In the pooled safety population (N=1127) from clinical trials comparing fulvestrant 500 mg to fulvestrant 250 mg, post-baseline increases of ≥1 CTC grade in either AST, ALT, or alkaline phosphatase were observed in >15% of patients receiving fulvestrant. Grade 3 to 4 increases were observed in 1 to 2% of patients. The incidence and severity of increased hepatic enzymes (ALT, AST, ALP) did not differ between the 250 mg and the 500 mg fulvestrant arms.

Comparison of Fulvestrant 500 mg and Anastrozole 1 mg (FALCON)

The safety of fulvestrant 500 mg versus anastrozole 1 mg was evaluated in FALCON. The data described below reflect exposure to fulvestrant in 228 out of 460 patients with HR-positive advanced breast cancer in postmenopausal women not previously treated with endocrine therapy who received at least one (1) dose of treatment in FALCON.

Permanent discontinuation associated with an adverse reaction occurred in 4 of 228 (1.8%) patients receiving fulvestrant, and in 3 of 232 (1.3%) patients receiving anastrozole. Adverse reactions leading to discontinuation for those patients receiving fulvestrant included drug hypersensitivity (0.9%), injection site hypersensitivity (0.4%) and elevated liver enzymes (0.4%).

The most common adverse reactions (≥10%) of any grade reported in patients in the fulvestrant arm were arthralgia, hot flash, fatigue and nausea.

Adverse reactions reported in patients who received fulvestrant in FALCON at an incidence of ≥5% in either treatment arm are listed in Table 2 , and laboratory abnormalities are listed in Table 3.

Table 2: Adverse Reactions in FALCON

Adverse Reactions

Fulvestrant 500 mg

N=228

Anastrozole 1 mg

N=232

All Grades

%

Grade 3 or 4

%

All Grades

%

Grade 3 or 4

%

Vascular Disorders

Hot flash

11

0

10

0

Gastrointestinal Disorders

Nausea

11

0

10

<1

Diarrhea

6

0

6

<1

Musculoskeletal and Connective Tissue Disorders

Arthralgia

17

0

10

0

Myalgia

7

0

3

0

Pain in extremity

6

0

4

0

Back pain

9

<1

6

0

General Disorders and Administration Site Conditions

Fatigue

11

<1

7

<1

Table 3: Laboratory Abnormalities in FALCON *

Laboratory Parameters

Fulvestrant 500 mg

N=228

Anastrozole 1mg

N=232

All Grades

%

Grade 3 or 4

%

All Grades

%

Grade 3 or 4

%

Alanine aminotransferase increased (ALT)

7

1

3

0

Aspartate aminotransferase increased (AST)

5

1

3

<1

*In FALCON, post-baseline increases of ≥1 CTC grade in either AST, ALT, or alkaline phosphatase were observed in >10% of patients receiving fulvestrant. Grade 3 to 4 increases were observed in 1% to 3% of patients.

Comparison of Fulvestrant 250 mg and Anastrozole 1 mg in Combined Trials (Studies 0020 and 0021)

The most commonly reported adverse reactions in the fulvestrant and anastrozole treatment groups were gastrointestinal symptoms (including nausea, vomiting, constipation, diarrhea and abdominal pain), headache, back pain, vasodilatation (hot flashes), and pharyngitis.

Injection site reactions with mild transient pain and inflammation were seen with fulvestrant and occurred in 7% of patients given the single 5 mL injection (Study 0020) and in 27% of patients given the 2 x 2.5 mL injections (Study 0021) in the two clinical trials that compared fulvestrant 250 mg and anastrozole 1 mg.

Table 4 lists adverse reactions reported with an incidence of 5% or greater, regardless of assessed causality, from the two controlled clinical trials comparing the administration of fulvestrant 250 mg intramuscularly once a month with anastrozole 1 mg orally once a day.

Table 4: Adverse Reactions in Studies 0020 and 0021 (≥5% from Combined Data)
Adverse Reactions Fulvestrant 250 mg N=423 % Anastrozole 1 mg N=423 %

Body as a Whole

68

68

Asthenia

23

27

Pain

19

20

Headache

15

17

Back Pain

14

13

Abdominal Pain

12

12

Injection Site Pain*

11

7

Pelvic Pain

10

9

Chest Pain

7

5

Flu Syndrome

7

6

Fever

6

6

Accidental Injury

5

6

Cardiovascular System

30

28

Vasodilatation

18

17

Digestive System

52

48

Nausea

26

25

Vomiting

13

12

Constipation

13

11

Diarrhea

12

13

Anorexia

9

11

Hemic and Lymphatic Systems

14

14

Anemia

5

5

Metabolic and Nutritional Disorders

18

18

Peripheral Edema

9

10

Musculoskeletal System

26

28

Bone Pain

16

14

Arthritis

3

6

Nervous System

34

34

Dizziness

7

7

Insomnia

7

9

Paresthesia

6

8

Depression

6

7

Anxiety

5

4

Respiratory System

39

34

Pharyngitis

16

12

Dyspnea

15

12

Cough Increased

10

10

Skin and Appendages

22

23

Rash

7

8

Sweating

5

5

Urogenital System

18

15

Urinary Tract Infection

6

4

*Including more severe injection site related sciatica, neuralgia, neuropathic pain, and peripheral neuropathy. All patients on fulvestrant received injections, but only those anastrozole patients who were in Study 0021 received placebo injections.

Combination Therapy

Combination Therapy with Palbociclib (PALOMA-3)

The safety of fulvestrant 500 mg plus palbociclib 125 mg/day versus fulvestrant plus placebo was evaluated in PALOMA-3. The data described below reflect exposure to fulvestrant plus palbociclib in 345 out of 517 patients with HR-positive, HER2-negative advanced or metastatic breast cancer who received at least 1 dose of treatment in PALOMA-3. The median duration of treatment for fulvestrant plus palbociclib was 10.8 months while the median duration of treatment for fulvestrant plus placebo arm was 4.8 months.

No dose reduction was allowed for fulvestrant in PALOMA-3. Dose reductions of palbociclib due to an adverse reaction of any grade occurred in 36% of patients receiving fulvestrant plus palbociclib.

Permanent discontinuation associated with an adverse reaction occurred in 19 of 345 (6%) patients receiving fulvestrant plus palbociclib, and in 6 of 172 (3%) patients receiving fulvestrant plus placebo. Adverse reactions leading to discontinuation for those patients receiving fulvestrant plus palbociclib included fatigue (0.6%), infections (0.6%), and thrombocytopenia (0.6%).

The most common adverse reactions (≥10%) of any grade reported in patients in the fulvestrant plus palbociclib arm by descending frequency were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, diarrhea, thrombocytopenia, vomiting, alopecia, rash, decreased appetite, and pyrexia.

The most frequently reported Grade ≥3 adverse reactions (≥5%) in patients receiving fulvestrant plus palbociclib in descending frequency were neutropenia and leukopenia.

Adverse reactions (≥10%) reported in patients who received fulvestrant plus palbociclib or fulvestrant plus placebo in PALOMA-3 are listed in Table 5 , and laboratory abnormalities are listed in Table 6.

Table 5: Adverse Reactions (≥10%)in PALOMA-3

*
Infections includes all reported preferred terms (PTs) that are part of the System Organ Class Infections and infestations.
Most common infections (≥1%) include: nasopharyngitis, upper respiratory infection, urinary tract infection, influenza, bronchitis, rhinitis, conjunctivitis, pneumonia, sinusitis, cystitis, oral herpes, respiratory tract infection, gastroenteritis, tooth infection, pharyngitis, eye infection, herpes simplex, paronychia.
Stomatitis includes: aphthous stomatitis, cheilitis, glossitis, glossodynia, mouth ulceration, mucosal inflammation, oral pain, oropharyngeal discomfort, oropharyngeal pain, stomatitis.
§
Grade 1 events – 17%; Grade 2 events – 1%.
Grade 1 events – 6%.
#
Rash includes: rash, rash maculo-papular, rash pruritic, rash erythematous, rash papular, dermatitis, dermatitis acneiform, toxic skin eruption.

Adverse Reactions

Fulvestrant plus Palbociclib

N=345

Fulvestrant plus Placebo

N=172

All Grades

Grade 3

Grade 4

All Grades

Grade 3

Grade 4

%

%

%

%

%

%

Infections and Infestations

Infections *

47

3

1

31

3

0

Blood and Lymphatic System Disorders

Neutropenia

83

55

11

4

1

0

Leukopenia

53

30

1

5

1

1

Anemia

30

4

0

13

2

0

Thrombocytopenia

23

2

1

0

0

0

Metabolism and Nutrition Disorders

Decreased appetite

16

1

0

8

1

0

Gastrointestinal Disorders

Nausea

34

0

0

28

1

0

Stomatitis

28

1

0

13

0

0

Diarrhea

24

0

0

19

1

0

Vomiting

19

1

0

15

1

0

Skin and Subcutaneous Tissue Disorders

Alopecia

18§

N/A

N/A

6

N/A

N/A

Rash #

17

1

0

6

0

0

General Disorders and Administration Site Conditions

Fatigue

41

2

0

29

1

0

Pyrexia

13

<1

0

5

0

0

Grading according to CTCAE v. 4.0.

CTCAE=Common Terminology Criteria for Adverse Events; N=number of patients; N/A=not applicable.

Additional adverse reactions occurring at an overall incidence of <10.0% of patients receiving fulvestrant plus palbociclib in PALOMA-3 included asthenia (7.5%), aspartate aminotransferase increased (7.5%), dysgeusia (6.7%), epistaxis (6.7%), lacrimation increased (6.4%), dry skin (6.1%), alanine aminotransferase increased (5.8%), vision blurred (5.8%), dry eye (3.8%), and febrile neutropenia (0.9%).

Table 6: Laboratory Abnormalities in PALOMA-3

Laboratory Parameters

Fulvestrant plus Palbociclib

N=345

Fulvestrant plus Placebo

N=172

All Grades

Grade 3

Grade 4

All Grades

Grade 3

Grade 4

%

%

%

%

%

%

WBC decreased

99

45

1

26

0

1

Neutrophils decreased

96

56

11

14

0

1

Anemia

78

3

0

40

2

0

Platelets decreased

62

2

1

10

0

0

Aspartate aminotransferase increased

43

4

0

48

4

0

Alanine aminotransferase increased

36

2

0

34

0

0

N=number of patients; WBC=white blood cells.

Combination Therapy with Abemaciclib (MONARCH 2)

The safety of fulvestrant (500 mg) plus abemaciclib (150 mg twice daily) versus fulvestrant plus placebo was evaluated in MONARCH 2. The data described below reflect exposure to fulvestrant in 664 patients with HR-positive, HER2-negative advanced breast cancer who received at least one dose of fulvestrant plus abemaciclib or placebo in MONARCH 2.

Median duration of treatment was 12 months for patients receiving fulvestrant plus abemaciclib and 8 months for patients receiving fulvestrant plus placebo.

Dose reductions due to an adverse reaction occurred in 43% of patients receiving fulvestrant plus abemaciclib. Adverse reactions leading to dose reductions ≥5% of patients were diarrhea and neutropenia. Abemaciclib dose reduction due to diarrhea of any grade occurred in 19% of patients receiving fulvestrant plus abemaciclib compared to 0.4% of patients receiving fulvestrant plus placebo. Abemaciclib dose reductions due to neutropenia of any grade occurred in 10% of patients receiving fulvestrant plus abemaciclib compared to no patients receiving fulvestrant plus placebo.

Permanent study treatment discontinuation due to an adverse event was reported in 9% of patients receiving fulvestrant plus abemaciclib and in 3% of patients receiving fulvestrant plus placebo. Adverse reactions leading to permanent discontinuation for patients receiving fulvestrant plus abemaciclib were infection (2%), diarrhea (1%), hepatotoxicity (1%), fatigue (0.7%), nausea (0.2%), abdominal pain (0.2%), acute kidney injury (0.2%), and cerebral infarction (0.2%).

Deaths during treatment or during the 30-day follow up, regardless of causality, were reported in 18 cases (4%) of fulvestrant plus abemaciclib treated patients versus 10 cases (5%) of fulvestrant plus placebo treated patients. Causes of death for patients receiving fulvestrant plus abemaciclib included: 7 (2%) patient deaths due to underlying disease, 4 (0.9%) due to sepsis, 2 (0.5%) due to pneumonitis, 2 (0.5%) due to hepatotoxicity, and one (0.2%) due to cerebral infarction.

The most common adverse reactions reported (≥20%) in the fulvestrant plus abemaciclib arm were diarrhea, fatigue, neutropenia, nausea, infections, abdominal pain, anemia, leukopenia, decreased appetite, vomiting, and headache (Table7). The most frequently reported (≥5%) Grade 3 or 4 adverse reactions were neutropenia, diarrhea, leukopenia, anemia, and infections.

Table 7: Adverse Reactions ≥10% of Patients Receiving Fulvestrant Plus Abemaciclib and ≥2% Higher Than Fulvestrant Plus Placebo in MONARCH 2

Adverse Reactions

Fulvestrant plus Abemaciclib

N=441

Fulvestrant plus Placebo

N=223

All Grades

%

Grade

3

%

Grade 4

%

All Grades

%

Grade

3

%

Grade 4

%

Gastrointestinal Disorders

Diarrhea

86

13

0

25

<1

0

Nausea

45

3

0

23

1

0

Abdominal pain

35

2

0

16

1

0

Vomiting

26

<1

0

10

2

0

Stomatitis

15

<1

0

10

0

0

Infections and Infestations

Infections†

43

5

<1

25

3

<1

Blood and Lymphatic System Disorders

Neutropenia

46

24

3

4

1

<1

Anemia§

29

7

<1

4

1

0

Leukopenia

28

9

<1

2

0

0

Thrombocytopenia#

16

2

1

3

0

<1

General Disorders and Administration Site Conditions

FatigueÞ

46

3

0

32

<1

0

Edema peripheral

12

0

0

7

0

0

Pyrexia

11

<1

<1

6

<1

0

Metabolism and Nutrition Disorders

Decreased appetite

27

1

0

12

<1

0

Respiratory, Thoracic and Mediastinal Disorders

Cough

13

0

0

11

0

0

Skin and Subcutaneous Tissue Disorders

Alopecia

16

0

0

2

0

0

Pruritus

13

0

0

6

0

0

Rash

11

1

0

4

0

0

Nervous System Disorders

Headache

20

1

0

15

<1

0

Dysgeusia

18

0

0

3

0

0

Dizziness

12

1

0

6

0

0

Investigations

Alanine aminotransferase increased

13

4

<1

5

2

0

Aspartate aminotransferase increased

12

2

0

7

3

0

Creatinine increased

12

<1

0

<1

0

0

Weight decreased

10

<1

0

2

<1

0

*Includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort, abdominal tenderness.

Includes upper respiratory tract infection, urinary tract infection, lung infection, pharyngitis, conjunctivitis, sinusitis, vaginal infection, sepsis.

Includes neutropenia, neutrophil count decreased.

§ Includes anemia, hematocrit decreased, hemoglobin decreased, red blood cell count decreased.

Includes leukopenia, white blood cell count decreased.

# Includes platelet count decreased, thrombocytopenia.

Þ Includes asthenia, fatigue.

Additional adverse reactions in MONARCH 2 include venous thromboembolic events (deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, subclavian vein thrombosis, axillary vein thrombosis, and DVT inferior vena cava), which were reported in 5% of patients treated with fulvestrant plus abemaciclib as compared to 0.9% of patients treated with fulvestrant plus placebo.

Table 8: Laboratory Abnormalities ≥10% in Patients Receiving Fulvestrant Plus Abemaciclib and ≥2% Higher Than Fulvestrant Plus Placebo in MONARCH 2
Laboratory Parameters Fulvestrant plus Abemaciclib N=441 Fulvestrant plus Placebo N=223
All Grades % Grade 3 % Grade 4 % All Grades % Grade 3 % Grade 4 %

Creatinine increased

98

1

0

74

0

0

White blood cell decreased

90

23

<1

33

<1

0

Neutrophil count decreased

87

29

4

30

4

<1

Anemia

84

3

0

33

<1

0

Lymphocyte count decreased

63

12

<1

32

2

0

Platelet count decreased

53

<1

1

15

0

0

Alanine aminotransferase increased

41

4

<1

32

1

0

Aspartate aminotransferase increased

37

4

0

25

4

<1

Combination Therapy with Ribociclib (MONALEESA-3)

The safety of fulvestrant 500 mg plus ribociclib 600 mg versus fulvestrant plus placebo was evaluated in MONALEESA-3. The data described below reflect exposure to fulvestrant plus ribociclib in 483 out of 724 postmenopausal patients with HR-positive, HER2-negative advanced or metastatic breast cancer for initial endocrine based therapy or after disease progression on endocrine therapy who received at least one dose of fulvestrant plus ribociclib or placebo in MONALEESA-3. Median duration of treatment was 15.8 months for fulvestrant plus ribociclib and 12 months for fulvestrant plus placebo.

Dose reductions due to adverse reactions occurred in 32% of patients receiving fulvestrant plus ribociclib and in 3% of patients receiving fulvestrant plus placebo. Among patients receiving fulvestrant plus ribociclib, 8% were reported to have permanently discontinued both fulvestrant plus ribociclib, and 9% were reported to have discontinued ribociclib alone due to ARs. Among patients receiving fulvestrant plus placebo, 4% were reported to have permanently discontinued both fulvestrant and placebo and 2% were reported to have discontinued placebo alone due to ARs.

Adverse reactions leading to treatment discontinuation of fulvestrant plus ribociclib (as compared to fulvestrant plus placebo) were ALT increased (5% vs. 0%), AST increased (3% vs. 0.6%), and vomiting (1% vs. 0%).

The most common adverse reactions (reported at a frequency ≥20% on the fulvestrant plus ribociclib arm and ≥2% higher than fulvestrant plus placebo) were neutropenia, infections, leukopenia, cough, nausea, diarrhea, vomiting, constipation, pruritus, and rash. The most frequently reported Grade ¾ adverse reactions (reported at a frequency ≥5%) in patients receiving fulvestrant plus ribociclib in descending frequency were neutropenia, leukopenia, infections, and abnormal liver function tests.

Adverse reactions and laboratory abnormalities occurring in patients in MONALEESA-3 are listed in Table 9 and Table 10 , respectively.

Table 9: Adverse Reactions Occurring in ≥10% and ≥2% higher than fulvestrant plus Placebo Arm in MONALEESA-3 (All Grades)
*
Infections; urinary tract infections; respiratory tract infections; gastroenteritis; sepsis (<1%).
Adverse Reactions
Fulvestrant plus Ribociclib N=483
Fulvestrant plus Placebo N=241

All Grades

%

Grade 3

%

Grade 4

%

All Grades

%

Grade 3

%

Grade 4

%

Infections and Infestations
Infections *

42

5

0

30

2

0

Blood and Lymphatic System Disorders
Neutropenia

69

46

7

2

0

0

Leukopenia

27

12

<1

<1

0

0

Anemia

17

3

0

5

2

0

Metabolism and Nutrition Disorders
Decreased appetite

16

<1

0

13

0

0

Nervous System Disorders
Dizziness

13

<1

0

8

0

0

Respiratory, Thoracic and Mediastinal Disorders
Cough

22

0

0

15

0

0

Dyspnea

15

1

<1

12

2

0

Gastrointestinal Disorders
Nausea

45

1

0

28

<1

0

Diarrhea

29

<1

0

20

<1

0

Vomiting

27

1

0

13

0

0

Constipation

25

<1

0

12

0

0

Abdominal pain

17

1

0

13

<1

0

Skin and Subcutaneous Tissue Disorders
Alopecia

19

0

0

5

0

0

Pruritus

20

<1

0

7

0

0

Rash

23

<1

0

7

0

0

General Disorders and Administration Site Conditions
Edema peripheral

15

0

0

7

0

0

Pyrexia

11

<1

0

7

0

0

Investigations
Alanine aminotransferase increased

15

7

2

5

<1

0

Aspartate aminotransferase increased

13

5

1

5

<1

0

Grading according to CTCAE 4.03.
CTCAE=Common Terminology Criteria for Adverse Events; N=number of patients

Additional adverse reactions in MONALEESA-3 for patients receiving fulvestrant plus ribociclib included asthenia (14%), dyspepsia (10%), thrombocytopenia (9%), dry skin (8%), dysgeusia (7%), electrocardiogram QT prolonged (6%), dry mouth (5%), vertigo (5%), dry eye (5%), lacrimation increased (4%), erythema (4%), hypocalcemia (4%), blood bilirubin increased (1%), and syncope (1%).

Table 10: Laboratory Abnormalities Occurring in ≥10% of Patients in MONALEESA-3

Laboratory parameters
Fulvestrant plus Ribociclib N=483
Fulvestrant plus Placebo N=241
All Grades

%

Grade 3

%

Grade 4

%

All Grades

%

Grade 3

%

Grade 4

%

Hematology
Leukocyte count decreased

95

25

<1

26

<1

0

Neutrophil count decreased

92

46

7

21

<1

0

Hemoglobin decreased

60

4

0

35

3

0

Lymphocyte count decreased

69

14

1

35

4

<1

Platelet count decreased

33

<1

1

11

0

0

Chemistry
Creatinine increased

65

<1

<1

33

<1

0

Gamma-glutamyl transferase increased

52

6

1

49

8

2

Aspartate aminotransferase increased

49

5

2

43

3

0

Alanine aminotransferase increased

44

8

3

37

2

0

Glucose serum decreased

23

0

0

18

0

0

Phosphorous decreased

18

5

0

8

<1

0

Albumin decreased

12

0

0

8

0

0

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