Lynparza

Last updated on RxList: 3/22/2021
Lynparza Side Effects Center

What Is Lynparza?

Lynparza (olaparib) is an inhibitor of the mammalian polyadenosine 5'-diphosphoribose polymerase (PARP) enzyme used as monotherapy in patients with deleterious or suspected deleterious germline BRCA mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.

What Are Side Effects of Lynparza?

Common side effects of Lynparza include:

Dosage for Lynparza

The recommended dose of Lynparza is 400 mg (eight 50 mg capsules) taken twice daily, for a total daily dose of 800 mg.

What Drugs, Substances, or Supplements Interact with Lynparza?

Lynparza may interact with inhibitors or inducers of CYP3A and other myelosuppressive anticancer agents. Tell your doctor all medications and supplements you use.

Lynparza During Pregnancy and Breastfeeding

Lynparza is not recommended for use during pregnancy. It may harm a fetus. It is unknown if this drug passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Lynparza (olaparib) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Signs of Cancer in Women: Symptoms You Can't Ignore See Slideshow
Lynparza Consumer Information

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Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

You may get infections more easily, even serious or fatal infections. Call your doctor right away if you have signs of infection such as:

  • fever, chills, weakness, feeling light-headed or very tired;
  • mouth sores, skin sores;
  • easy bruising, unusual bleeding;
  • pain or burning when you urinate, blood in your urine or stools;
  • pale skin, cold hands and feet
  • weight loss; or
  • cough, wheezing, shortness of breath.

Your cancer treatments may be delayed if you have certain side effects.

Some people who take olaparib with a gonadotropin-releasing hormone (GnRH) medicine may develop a blood clot in the leg or in the lung. Call your doctor if you have pain or swelling in your arm or leg, shortness of breath, chest pain, rapid breathing, or fast heartbeats.

Common side effects may include:

  • low blood cell counts;
  • pain and burning when you urinate, painful urination;
  • nausea, vomiting, upper stomach pain, diarrhea;
  • heartburn, indigestion, loss of appetite;
  • dizziness, feeling weak or tired;
  • headache;
  • cough, shortness of breath; or
  • altered sense of taste.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Lynparza (Olaparib Capsules for Oral Administration)

QUESTION

Where does ovarian cancer occur? See Answer
Lynparza Professional Information

SIDE EFFECTS

The following adverse reactions are discussed elsewhere in the labeling:

  • Myelodysplastic Syndrome/Acute Myeloid Leukemia [see WARNINGS AND PRECAUTIONS]
  • Pneumonitis [see WARNINGS AND PRECAUTIONS]
  • Venous Thromboembolic Events [see WARNINGS AND PRECAUTIONS]

Clinical Trial Experience

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

The data described in the WARNINGS AND PRECAUTIONS reflect exposure to Lynparza as a single agent in 2351 patients; 1585 patients with exposure to 300 mg twice daily tablet dose including five controlled, randomized, trials (SOLO-1, SOLO-2, OlympiAD, POLO, and PROfound) and to 400 mg twice daily capsule dose in 766 patients in other trials that were pooled to conduct safety analyses. In these trials, 55% of patients were exposed for 6 months or longer and 31% were exposed for greater than one year in the Lynparza group.

In this pooled safety population, the most common adverse reactions in ≥10% of patients were nausea (60%), fatigue (55%), anemia (37%), vomiting (34%), diarrhea (25%), decreased appetite (23%), headache (16%), neutropenia (15%), dysgeusia (15%), cough (15%), dyspnea (14%), dizziness (12%), dyspepsia (12%), leukopenia (11%), thrombocytopenia (11%), and abdominal pain upper (10%).

First-Line Maintenance Treatment Of BRCA-mutated Advanced Ovarian Cancer

SOLO-1

The safety of Lynparza for the maintenance treatment of patients with BRCA-mutated advanced ovarian cancer following first-line treatment with platinum-based chemotherapy was investigated in SOLO-1 [see Clinical Studies]. Patients received Lynparza tablets 300 mg orally twice daily (n=260) or placebo (n=130) until disease progression or unacceptable toxicity. The median duration of study treatment was 25 months for patients who received Lynparza and 14 months for patients who received placebo.

Among patients who received Lynparza, dose interruptions due to an adverse reaction of any grade occurred in 52% and dose reductions due to an adverse reaction occurred in 28%. The most frequent adverse reactions leading to dose interruption or reduction of Lynparza were anemia (23%), nausea (14%), and vomiting (10%). Discontinuation due to adverse reactions occurred in 12% of patients receiving Lynparza. The most frequent adverse reactions that led to discontinuation of Lynparza were fatigue (3.1%), anemia (2.3%), and nausea (2.3%).

Tables 2 and 3 summarize adverse reactions and laboratory abnormalities in SOLO-1.

Table 2 : Adverse Reactions* in SOLO-1 (≥10% of Patients Who Received Lynparza)

Adverse Reaction Lynparza tablets
n=260
Placebo
n=130
All Grades (%) Grades 3 - 4 (%) All Grades (%) Grades 3 - 4 (%)
Gastrointestinal Disorders
Nausea 77 1 38 0
Abdominal pain† 45 2 35 1
Vomiting 40 0 15 1
Diarrhea‡ 37 3 26 0
Constipation 28 0 19 0
Dyspepsia 17 0 12 0
Stomatitis§ 11 0 2 0
General Disorders and Administration Site Conditions
Fatigue¶ 67 4 42 2
Blood and Lymphatic System Disorders
Anemia 38 21 9 2
Neutropenia# 17 6 7 3
LeukopeniaÞ 13 3 8 0
Thrombocytopenia? 11 1 4 2
Infections and Infestations
Upper respiratory tract infection/ influenza/nasopharyngitis/bronchitis 28 0 23 0
UTIà 13 1 7 0
Nervous System Disorders
Dysgeusia 26 0 4 0
Dizziness 20 0 15 1
Metabolism and Nutrition Disorders
Decreased appetite 20 0 10 0
Respiratory, Thoracic and Mediastinal Disorders
Dyspneaè 15 0 6 0
* Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.
† Includes abdominal pain, abdominal pain lower, abdominal pain upper, abdominal distension, abdominal discomfort, and abdominal tenderness.
‡ Includes colitis, diarrhea, and gastroenteritis.
§ Includes stomatitis, aphthous ulcer; and mouth ulceration.
¶ Includes asthenia, fatigue, lethargy, and malaise.
# Includes neutropenia, and febrile neutropenia.
Þ Includes leukopenia, and white blood cell count decreased.
? Includes platelet count decreased, and thrombocytopenia.
à Includes urosepsis, urinary tract infection, urinary tract pain, nd pyuria.
è Includes dyspnea, and dyspnea exertional.

In addition, the adverse reactions observed in SOLO-1 that occurred in <10% of patients receiving Lynparza were increased blood creatinine (8%), lymphopenia (6%), hypersensitivity (2%), dermatitis (1%), and increased mean cell volume (0.4%).

Table 3 : Laboratory Abnormalities Reported in ≥25% of Patients in SOLO-1

Laboratory Parameter* Lynparza tablets n†=260 Placebo n†=130
Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%)
Decrease in hemoglobin 87 19 63 2
Increase in mean corpuscular volume 87 - 43 -
Decrease in leukocytes 70 7 52 1
Decrease in lymphocytes 67 14 29 5
Decrease in absolute neutrophil count 51 9 38 6
Decrease in platelets 35 1 20 2
Increase in serum creatinine 34 0 18 0
* Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
† This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.

First-line Maintenance Treatment Of HRD-positive Advanced Ovarian Cancer In Combination With Bevacizumab
PAOLA-1

The safety of Lynparza in combination with bevacizumab for the maintenance treatment of patients with advanced ovarian cancer following first-line treatment containing platinum-based chemotherapy and bevacizumab was investigated in PAOLA-1 [see Clinical Studies]. This study was a placebo-controlled, double-blind study in which 802 patients received either Lynparza 300 mg BID in combination with bevacizumab (n=535) or placebo in combination with bevacizumab (n=267) until disease progression or unacceptable toxicity. The median duration of treatment with Lynparza was 17.3 months and 11 months for bevacizumab post-randomization on the Lynparza/bevacizumab arm.

Fatal adverse reactions occurred in 1 patient due to concurrent pneumonia and aplastic anemia. Serious adverse reactions occurred in 31% of patients who received Lynparza/bevacizumab. Serious adverse reactions in >5% of patients included hypertension (19%) and anemia (17%).

Dose interruptions due to an adverse reaction of any grade occurred in 54% of patients receiving Lynparza/bevacizumab and dose reductions due to an adverse reaction occurred in 41% of patients who received Lynparza/bevacizumab.

The most frequent adverse reactions leading to dose interruption in the Lynparza/bevacizumab arm were anemia (21%), nausea (7%), vomiting (3%), and fatigue (3%), and the most frequent adverse reactions leading to reduction in the Lynparza/bevacizumab arm were anemia (19%), nausea (7%), and fatigue (4%).

Discontinuation due to adverse reactions occurred in 20% of patients receiving Lynparza/bevacizumab. Specific adverse reactions that most frequently led to discontinuation in patients treated with Lynparza/bevacizumab were anemia (4%) and nausea (3%).

Tables 4 and 5 summarize adverse reactions and laboratory abnormalities in PAOLA-1, respectively.

Table 4 : Adverse Reactions* Occurring in ≥10% of Patients Treated with Lynparza/bevacizumab in PAOLA-1 and at ≥5% Frequency Compared to the Placebo/bevacizumab Arm

Adverse Reactions Lynparza/ bevacizum ab
n=535
Placebo/ bevacizumab
n=267
Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%)
General Disorders and Administration Site Conditions
Fatigue (including asthenia)† 53 5 32 1.5
Gastrointestinal Disorders
Nausea 53 2.4 22 0.7
Vomiting 22 1.7 11 1.9
Blood and Lymphatic Disorders
Anemia‡ 41 17 10 0.4
Lymphopenia§ 24 7 9 1.1
Leukopenia|| 18 1.9 10 1.5
* Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.
† Includes asthenia, and fatigue.
‡ Includes anemia, anemia macrocytic, erythropenia, haematocrit decreased, haemoglobin decreased, normochromic anemia, normochromic normocytic anemia, normocytic anemia, and red blood cell count decreased. Includes B-lymphocyte count decreased, lymphocyte count decreased, lymphopenia, and T-lymphocyte count decreased.
§ Includes B-lymphocyte count decreased, lymphocyte count decreased, lymphopenia, and T-lymphocyte count decreased.
|| Includes leukopenia, and white blood cell count decreased.

The most common adverse reactions (≥ 10%) for patients receiving Lynparza/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia, vomiting (22%), diarrhea (18%), neutropenia (18%), leukopenia (18%), urinary tract infection (15%), and headache (14%).

The adverse reactions that occurred in <10% of patients receiving Lynparza/bevacizumab were dysgeusia (8%), dyspnea (8%), stomatitis (5%), dyspepsia (4.3%), erythema (3%), dizziness (2.6%), and hypersensitivity (1.7%).

In addition, venous thromboembolic events occurred more commonly in patients receiving Lynparza/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).

Table 5 : Laboratory Abnormalities Reported in ≥25% of Patients in PAOLA-1*

Laboratory Parameter† Lynparza /bevacizum ab
n†=535
Placebo /bevacizumab
n‡=267
Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%)
Decrease in hemoglobin 79 13 55 0.4
Decrease in lymphocytes 63 10 42 3.0
Increase in serum creatinine 61 0.4 36 0.4
Decrease in leukocytes 59 3.4 45 2.2
Decrease in absolute neutrophil count 35 7 30 3.7
Decrease in platelets 35 2.4 28 0.4
* Reported within 30 days of the last dose.
† Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
‡ This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.

Maintenance Treatment Of Recurrent Ovarian Cancer

SOLO-2

The safety of Lynparza for the maintenance treatment of patients with platinum sensitive gBRCAm ovarian cancer was investigated in SOLO-2 [see Clinical Studies]. Patients received Lynparza tablets 300 mg orally twice daily (n=195) or placebo (n=99) until disease progression or unacceptable toxicity. The median duration of study treatment was 19.4 months for patients who received Lynparza and 5.6 months for patients who received placebo.

Among patients who received Lynparza, dose interruptions due to an adverse reaction of any grade occurred in 45% and dose reductions due to an adverse reaction occurred in 27%. The most frequent adverse reactions leading to dose interruption or reduction of Lynparza were anemia (22%), neutropenia (9%), and fatigue/asthenia (8%). Discontinuation due to an adverse reaction occurred in 11% of patients receiving Lynparza.

Tables 6 and 7 summarize adverse reactions and laboratory abnormalities in SOLO-2.

Table 6 : Adverse Reactions* in SOLO-2 (≥20% of Patients Who Received Lynparza)

Adverse Reaction Lynparza tablets
n=195
Placebo
n=99
Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%)
Gastrointestinal Disorders
Nausea 76 3 33 0
Vomiting 37 3 19 1
Diarrhea 33 2 22 0
Stomatitis† 20 1 16 0
General Disorders and Administration Site Conditions
Fatigue including asthenia 66 4 39 2
Blood and Lymphatic Disorders
Anemia‡ 44 20 9 2
Infections and Infestations
Nasopharyngitis/URI/sinusitis/ rhinitis/influenza 36 0 29 0
Musculoskeletal and Connective Tissue Disorders
Arthralgia/myalgia 30 0 28 0
Nervous System Disorders
Dysgeusia 27 0 7 0
Headache 26 1 14 0
Metabolism and Nutrition Disorders
Decreased appetite 22 0 11 0
* Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.
† Represents grouped term consisting of abscess oral, aphthous ulcer, gingival abscess, gingival disorder, gingival pain, gingivitis, mouth ulceration, mucosal infection, mucosal inflammation, oral candidiasis, oral discomfort, oral herpes, oral infection, oral mucosal erythema, oral pain, oropharyngeal discomfort, and oropharyngeal pain.
‡ Represents grouped term consisting of anemia, hematocrit decreased, hemoglobin decreased, iron deficiency, mean cell volume increased and red blood cell count decreased.

In addition, the adverse reactions observed in SOLO-2 that occurred in <20% of patients receiving Lynparza were neutropenia (19%), cough (18%), leukopenia (16%), hypomagnesemia (14%), thrombocytopenia (14%), dizziness (13%), dyspepsia (11%), increased creatinine (11%), edema (8%), rash (6%), and lymphopenia (1%).

Table 7 : Laboratory Abnormalities Reported in ≥25% of Patients in SOLO-2

Laboratory Parameter* Lynparza tablets
n†=195
Placebo
n†=99
Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%)
Increase in mean corpuscular volume‡ 89 - 52 -
Decrease in hemoglobin 83 17 69 0
Decrease in leukocytes 69 5 48 1
Decrease in lymphocytes 67 11 37 1
Decrease in absolute neutrophil count 51 7 34 3
Increase in serum creatinine 44 0 29 0
Decrease in platelets 42 2 22 1
* Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
† This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.
‡ Represents the proportion of subjects whose mean corpuscular volume was > upper limit of normal (ULN).

Study 19

The safety of Lynparza as maintenance monotherapy was evaluated in patients with platinum sensitive ovarian cancer who had received 2 or more previous platinum containing regimens in Study 19 [see Clinical Studies]. Patients received Lynparza capsules 400 mg orally twice daily (n=136) or placebo (n=128). At the time of final analysis, the median duration of exposure was 8.7 months in patients who received Lynparza and 4.6 months in patients who received placebo.

Adverse reactions led to dose interruptions in 35% of patients receiving Lynparza; dose reductions in 26% and discontinuation in 6% of patients receiving Lynparza.

Tables 8 and 9 summarize adverse reactions and laboratory abnormalities in Study 19.

Table 8 : Adverse Reactions* in Study 19 (≥20% of Patients Who Received Lynparza)

Adverse Reaction Lynparza capsules
n=136
Placebo
n=128
Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%)
Gastrointestinal Disorders
Nausea 71 2 36 0
Vomiting 35 2 14 1
Diarrhea 28 2 25 2
Constipation 22 1 12 0
Dyspepsia 20 0 9 0
General Disorders and Administration Site Conditions
Fatigue (including asthenia) 63 9 46 3
Blood and Lymphatic Disorders
Anemia† 23 7 7 1
Infections and Infestations
Respiratory tract infection 22 2 11 0
Metabolism and Nutrition Disorders
Decreased appetite 21 0 13 0
Nervous System Disorders
Headache 21 0 13 1
* Graded according to NCI CTCAE v4.0.
† Represents grouped terms of related terms that reflect the medical concept of the adverse reaction.

In addition, the adverse reactions in Study 19 that occurred in <20% of patients receiving Lynparza were dysgeusia (16%), dizziness (15%), dyspnea (13%), pyrexia (10%), stomatitis (9%), edema (9%), increase in creatinine (7%), neutropenia (5%), thrombocytopenia (4%), leukopenia (2%), and lymphopenia (1%).

Table 9 : Laboratory Abnormalities Reported in ≥25% of Patients in Study 19

Laboratory Parameter* Lynparza capsules
n†=136
Placebo
n†=129
Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%)
Decrease in hemoglobin 82 8 58 1
Increase in mean corpuscular volume‡ 82 - 51 -
Decrease in leukocytes 58 4 37 2
Decrease in lymphocytes 52 10 32 3
Decrease in absolute neutrophil count 47 7 40 2
Increase in serum creatinine 45 0 14 0
Decrease in platelets 36 4 18 0
* Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
† This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.
‡ Represents the proportion of subjects whose mean corpuscular volume was > ULN.

Advanced Germline BRCA-mutated Ovarian Cancer After 3 Or More Lines Of Chemotherapy

Pooled Data

The safety of Lynparza was investigated in 223 patients (pooled from 6 studies) with gBRCAm advanced ovarian cancer who had received 3 or more prior lines of chemotherapy [see Clinical Studies]. Patients received Lynparza capsules 400 mg orally twice daily until disease progression or unacceptable tolerability. The median exposure to Lynparza in these patients was 5.2 months.

There were 8 (4%) patients with adverse reactions leading to death, two were attributed to acute leukemia, and one each was attributed to COPD, cerebrovascular accident, intestinal perforation, pulmonary embolism, sepsis, and suture rupture. Adverse reactions led to dose interruption in 40% of patients, dose reduction in 4%, and discontinuation in 7%.

Tables 10 and 11 summarize the adverse reactions and laboratory abnormalities from the pooled studies.

Table 10 : Adverse Reactions Reported in Pooled Data (≥20% of Patients Who Received Lynparza)

Adverse Reaction Lynparza capsules
n=223
Grades 1-4 (%) Grades 3-4 (%)
General Disorders
Fatigue/asthenia 66 8
Gastrointestinal Disorders
Nausea 64 3
Vomiting 43 4
Diarrhea 31 1
Dyspepsia 25 0
Decreased appetite 22 1
Blood and Lymphatic Disorders
Anemia 34 18
Infections and Infestations
Nasopharyngitis/URI 26 0
Musculoskeletal and Connective Tissue Disorders
Arthralgia/musculoskeletal pain 21 0
Myalgia 22 0

Table 11 : Laboratory Abnormalities Reported in ≥25% of Patients in Pooled Data

Laboratory Parameter* Lynparza capsules
n†=223
Grades 1-4 (%) Grades 3-4 (%)
Decrease in hemoglobin 90 15
Mean corpuscular volume elevation 57 -
Decrease in lymphocytes 56 17
Decrease in platelets 30 3
Increase in creatinine 30 2
Decrease in absolute neutrophil count 25 7
* Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
† This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.

The following adverse reactions and laboratory abnormalities have been identified in ≥10 to <20% of the 223 patients receiving Lynparza and not included in the table: cough (16%), constipation (16%), dysgeusia (16%), headache (15%), peripheral edema (14%), back pain (14%), urinary tract infection (14%), dyspnea (13%), and dizziness (11%).

The following adverse reactions and laboratory abnormalities have been identified in <10% of the 223 patients receiving Lynparza and not included in the table: leukopenia (9%), pyrexia (8%), peripheral neuropathy (5%), hypomagnesemia (5%), rash (5%), stomatitis (4%), and venous thrombosis (including pulmonary embolism) (1%).

Germline BRCA-mutated HER2-negative Metastatic Breast Cancer

OlympiAD

The safety of Lynparza was evaluated in gBRCAm patients with HER2-negative metastatic breast cancer who had previously received up to two lines of chemotherapy for the treatment of metastatic disease in OlympiAD [see Clinical Studies]. Patients received either Lynparza tablets 300 mg orally twice daily (n=205) or a chemotherapy (capecitabine, eribulin, or vinorelbine) of the healthcare provider's choice (n=91) until disease progression or unacceptable toxicity. The median duration of study treatment was 8.2 months in patients who received Lynparza and 3.4 months in patients who received chemotherapy.

Among patients who received Lynparza, dose interruptions due to an adverse reaction of any grade occurred in 35% and dose reductions due to an adverse reaction occurred in 25%. Discontinuation due to an adverse reaction occurred in 5% of patients receiving Lynparza.

Tables 12 and 13 summarize the adverse reactions and laboratory abnormalities in OlympiAD.

Table 12 : Adverse Reactions* in OlympiAD (≥20% of Patients Who Received Lynparza)

Adverse Reaction Lynparza tablets
n=205
Chemotherapy
n=91
Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%)
Gastrointestinal Disorders
Nausea 58 0 35 1
Vomiting 30 0 15 1
Diarrhea 21 1 22 0
Blood and Lymphatic Disorders
Anemia† 40 16 26 4
Neutropenia‡ 27 9 50 26
Leukopenia§ 25 5 31 13
General Disorders and Administration Site Conditions
Fatigue (including asthenia) 37 4 36 1
Infections and Infestations
Respiratory tract infection|| 27 1 22 0
Nervous System Disorders
Headache 20 1 15 2
* Graded according to NCI CTCAE v4.0.
† Represents grouped terms consisting of anemia (anemia erythropenia, hematocrit decreased, hemoglobin decreased and red blood cell count decreased).
‡Represents grouped terms consisting of neutropenia (febrile neutropenia, granulocyte count decreased, granulocytopenia, neutropenia, neutropenic infection, neutropenic sepsis, and neutrophil count decreased).
§ Represents grouped terms consisting of leukopenia (leukopenia and white blood cell count decreased).
|| Represents grouped terms consisting of bronchitis, influenza, lower respiratory tract infection, nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis, sinusitis, upper respiratory tract infection, and upper respiratory tract infection bacterial.

In addition, adverse reactions in OlympiAD that occurred in <20% of patients receiving Lynparza were cough (18%), decreased appetite (16%), thrombocytopenia (11%), dysgeusia (9%), lymphopenia (8%), dyspepsia (8%), dizziness (7%), stomatitis (7%), upper abdominal pain (7%), rash (5%), increase in serum creatinine (3%), and dermatitis (1%).

Table 13 : Laboratory Abnormalities Reported in ≥25% of Patients in OlympiAD

Laboratory Parameter* Lynparza tablets
n†= 205
Chemotherapy
n†= 91
Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%)
Decrease in hemoglobin 82 17 66 3
Decrease in lymphocytes 73 21 63 3
Decrease in leukocytes 71 8 70 23
Increase in mean corpuscular volume‡ 71 - 33 -
Decrease in absolute neutrophil count 46 11 65 38
Decrease in platelets 33 3 28 0
* Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
† This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.
‡ Represents the proportion of subjects whose mean corpuscular volume was > ULN.

First-line Maintenance Treatment Of Germline BRCA-mutated Metastatic Pancreatic Adenocarcinoma

POLO

The safety of Lynparza as maintenance treatment of germline BRCA-mutated metastatic pancreatic adenocarcinoma following first-line treatment with platinum-based chemotherapy was evaluated in POLO [see Clinical Studies]. Patients received Lynparza tablets 300 mg orally twice daily (n=90) or placebo (n=61) until disease progression or unacceptable toxicity. Among patients receiving Lynparza, 34% were exposed for 6 months or longer and 25% were exposed for greater than one year.

Among patients who received Lynparza, dosage interruptions due to an adverse reaction of any grade occurred in 35% and dosage reductions due to an adverse reaction occurred in 17%. The most frequent adverse reactions leading to dosage interruption or reduction in patients who received Lynparza were anemia (11%), vomiting (5%), abdominal pain (4%), asthenia (3%), and fatigue (2%). Discontinuation due to adverse reactions occurred in 6% of patients receiving Lynparza. The most frequent adverse reaction that led to discontinuation of Lynparza was fatigue (2.2%).

Tables 14 and 15 summarize the adverse reactions and laboratory abnormalities in patients in POLO.

Table 14 : Adverse Reactions* in POLO (Occurring in ≥10% of Patients who Received Lynparza)

Adverse Reaction Lynparza tablets
(n=91)†
Placebo
(n=60)†
All Grades (%) Grades 3 - 4 (%) All Grades (%) Grades 3 - 4 (%)
General Disorders and Administration Site Conditions
Fatigue‡ 60 5 35 2
Gastrointestinal Disorders
Nausea 45 0 23 2
Abdominal pain^ 34 2 37 5
Diarrhea 29 0 15 0
Constipation 23 0 10 0
Vomiting 20 1 15 2
Stomatitis§ 10 0 5 0
Blood and Lymphatic System Disorders
Anemia 27 11 17 3
Thrombocytopenia|| 14 3 7 0
Neutropenia¶ 12 4 8 3
Metabolism and Nutrition Disorders
Decreased appetite 25 3 7 0
Musculoskeletal and Connective Tissue Disorders
Back pain 19 0 17 2
Arthralgia 15 1 10 0
Skin and Subcutaneous Tissue Disorder
Rash# 15 0 5 0
Respiratory, Thoracic and Mediastinal Disorders
Dyspnea** 13 0 5 2
Infections and Infestations
Nasopharyngitis 12 0 3 0
Nervous System Disorders
Dysgeusia 11 0 5 0
* Graded according to NCI CTCAE, version 4.0
† This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.
‡ Includes asthenia and fatigue
^ Includes abdominal pain, abdominal pain upper, abdominal pain lower
§ Includes stomatitis and mouth ulceration
|| Includes platelets count decreased and thrombocytopenia
¶ Includes neutropenia, febrile neutropenia and neutrophil count decreased
# Includes rash erythematous, rash macular and rash maculo-papular
**Includes dyspnea and dyspnea exertional

In addition, the adverse reactions observed in POLO that occurred in <10% of patients receiving Lynparza were cough (9%), abdominal pain upper (7%), blood creatinine increased (7%), dizziness (7%), headache (7%), dyspepsia (5%), leukopenia (5%), hypersensitivity (2%), and lymphopenia (2%).

Table 15 : Laboratory Abnormalities Reported in ≥25% of Patients in POLO

Laboratory Parameter* Lynparza tablets
n†=91
Placebo
n†=60
Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%)
Increase in serum creatinine 99 2 85 0
Decrease in hemoglobin 86 11 65 0
Increase in mean corpuscular volume‡ 71 - 30 -
Decrease in lymphocytes 61 9 27 0
Decrease in platelets 56 2 39 0
Decrease in leukocytes 50 3 23 0
Decrease in absolute neutrophil count 25 3 10 0
* Patients were allowed to enter POLO with hemoglobin ≥9 g/dL (CTCAE Grade 2) and other laboratory values of CTCAE Grade 1.
† This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.
‡ Represents the proportion of subjects whose mean corpuscular volume was > ULN.

HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

PROfound

The safety of Lynparza as monotherapy was evaluated in patients with mCRPC and HRR gene mutations who have progressed following prior treatment with enzalutamide or abiraterone in PROfound [see Clinical Studies]. This study was a randomized, open-label, multi-center study in which 386 patients received either Lynparza tablets 300 mg orally twice daily (n=256) or investigator's choice of enzalutamide or abiraterone acetate (n=130) until disease progression or unacceptable toxicity. Among patients receiving Lynparza, 62% were exposed for 6 months or longer and 20% were exposed for greater than one year.

Fatal adverse reactions occurred in 4% of patients treated with Lynparza. These included pneumonia (1.2%), cardiopulmonary failure (0.4%), aspiration pneumonia (0.4%), intestinal diverticulum (0.4%), septic shock (0.4%), Budd-Chiari Syndrome (0.4%), sudden death (0.4%), and acute cardiac failure (0.4%).

Serious adverse reactions occurred in 36% of patients receiving Lynparza. The most frequent serious adverse reactions (≥2%) were anemia (9%), pneumonia (4%), pulmonary embolism (2%), fatigue/asthenia (2%), and urinary tract infection (2%).

Dose interruptions due to an adverse reaction of any grade occurred in 45% of patients receiving Lynparza; dose reductions due to an adverse reaction occurred in 22% of Lynparza patients. The most frequent adverse reactions leading to dose interruption of Lynparza were anemia (25%) and thrombocytopenia (6%) and the most frequent adverse reaction leading to reduction of Lynparza was anemia (16%). Discontinuation due to adverse reactions occurred in 18% of Lynparza. The adverse reaction that most frequently led to discontinuation of Lynparza was anemia (7%).

Tables 16 and 17 summarize the adverse reactions and laboratory abnormalities, respectively, in patients in PROfound.

Table 16 : Adverse Reactions* Reported in ≥10% of Patients in PROfound

Adverse Reactions Lynparza tablets
n=256
Enzalutamide or abiraterone
n=130
Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%)
Blood and lymphatic disorders
Anemia† 46 21 15 5
Thrombocytopenia‡ 12 4 3 0
Gastrointestinal disorders
Nausea 41 1 19 0
Diarrhea 21 1 7 0
Vomiting 18 2 12 1
General disorders and administration site conditions
Fatigue (including asthenia) 41 3 32 5
Metabolism and nutrition disorders
Decreased appetite 30 1 18 1
Respiratory, thoracic, and mediastinal disorders
Cough 11 0 2 0
Dyspnea 10 2 3 0
* Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03
† Includes anemia and hemoglobin decreased
‡ Includes platelet count decreased and thrombocytopenia

In addition, adverse reactions of clinical relevance in PROfound that occurred in <10% of patients receiving Lynparza were neutropenia (9%), venous thromboembolic events (7%), dizziness (7%), dysgeusia (7%), dyspepsia (7%), headache (6%), pneumonia (5%), stomatitis (5%), rash (4%), blood creatinine increase (4%), pneumonitis (2%), upper abdominal pain (2%), and hypersensitivity (1%).

Table 17 : Laboratory Abnormalities Reported in ≥25% of Patients in PROfound

Laboratory Parameter* Lynparza tablets
n†= 256
Enzalutamide or abiraterone
n†=130
Grades 1-4
n= 247 (%)
Grades 3-4
n=247 (%)
Grades 1-4
n=124 (%)
Grades 3-4
n=124 (%)
Decrease in hemoglobin 242 (98) 33 (13) 91 (73) 5 (4)
Decrease in lymphocytes 154 (62) 57 (23) 42 (34) 16 (13)
Decrease in leukocytes 130 (53) 9 (4) 26 (21) 0
Decrease in absolute neutrophil count 83 (34) 8 (3) 11 (9) 0
* Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
† This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Lynparza. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: Hypersensitivity (rash/dermatitis/angioedema).

DRUG INTERACTIONS

Use With Anticancer Agents

Clinical studies of Lynparza with other myelosuppressive anticancer agents, including DNA damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

Effect Of Other Drugs On Lynparza

Strong And Moderate CYP3A Inhibitors

Coadministration of CYP3A inhibitors can increase olaparib concentrations, which may increase the risk for adverse reactions [see CLINICAL PHARMACOLOGY]. Avoid coadministration of strong or moderate CYP3A inhibitors. If the strong or moderate inhibitor must be coadministered, reduce the dose of Lynparza [see DOSAGE AND ADMINISTRATION].

Strong And Moderate CYP3A Inducers

Concomitant use with a strong or moderate CYP3A inducer decreased olaparib exposure, which may reduce Lynparza efficacy [see CLINICAL PHARMACOLOGY]. Avoid coadministration of strong or moderate CYP3A inducers.

SIDE EFFECTS

The following adverse reactions are discussed elsewhere in the labeling:

  • Myelodysplastic Syndrome/Acute Myeloid Leukemia [see WARNINGS AND PRECAUTIONS]
  • Pneumonitis [see WARNINGS AND PRECAUTIONS]
  • Venous Thromboembolic Events [see WARNINGS AND PRECAUTIONS]

Clinical Trial Experience

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

The data described in the WARNINGS AND PRECAUTIONS reflect exposure to Lynparza as a single agent in 2351 patients; 1585 patients with exposure to 300 mg twice daily tablet dose including five controlled, randomized, trials (SOLO-1, SOLO-2, OlympiAD, POLO, and PROfound) and to 400 mg twice daily capsule dose in 766 patients in other trials that were pooled to conduct safety analyses. In these trials, 55% of patients were exposed for 6 months or longer and 31% were exposed for greater than one year in the Lynparza group.

In this pooled safety population, the most common adverse reactions in ≥10% of patients were nausea (60%), fatigue (55%), anemia (37%), vomiting (34%), diarrhea (25%), decreased appetite (23%), headache (16%), neutropenia (15%), dysgeusia (15%), cough (15%), dyspnea (14%), dizziness (12%), dyspepsia (12%), leukopenia (11%), thrombocytopenia (11%), and abdominal pain upper (10%).

First-Line Maintenance Treatment Of BRCA-Mutated Advanced Ovarian Cancer

SOLO-1

The safety of Lynparza for the maintenance treatment of patients with BRCA-mutated advanced ovarian cancer following first-line treatment with platinum-based chemotherapy was investigated in SOLO-1 [see Clinical Studies]. Patients received Lynparza tablets 300 mg orally twice daily (n=260) or placebo (n=130) until disease progression or unacceptable toxicity. The median duration of study treatment was 25 months for patients who received Lynparza and 14 months for patients who received placebo. Among patients who received Lynparza, dose interruptions due to an adverse reaction of any grade occurred in 52% and dose reductions due to an adverse reaction occurred in 28%. The most frequent adverse reactions leading to dose interruption or reduction of Lynparza were anemia (23%), nausea (14%), and vomiting (10%). Discontinuation due to adverse reactions occurred in 12% of patients receiving Lynparza. The most frequent adverse reactions that led to discontinuation of Lynparza were fatigue (3.1%), anemia (2.3%), and nausea (2.3%).

Tables 2 and 3 summarize adverse reactions and laboratory abnormalities in SOLO-1.

Table 2 - Adverse Reactions* in SOLO-1 (≥10% of Patients Who Received Lynparza)

Adverse Reaction Lynparza tablets
n=260
Placebo
n=130
All Grades
(%)
Grades
3 – 4 (%)
All Grades
(%)
Grades
3 – 4 (%)
Gastrointestinal Disorders
  Nausea 77 1 38 0
  Abdominal pain 45 2 35 1
  Vomiting 40 0 15 1
  Diarrhea 37 3 26 0
  Constipation 28 0 19 0
  Dyspepsia 17 0 12 0
  Stomatitis§ 11 0 2 0
General Disorders and Administration Site Conditions
  Fatigue 67 4 42 2
Blood and Lymphatic System Disorders
  Anemia 38 21 9 2
  Neutropenia# 17 6 7 3
  LeukopeniaÞ 13 3 8 0
  Thrombocytopenia? 11 1 4 2
Infections and Infestations
  Upper respiratory tract infection/ influenza/ nasopharyngitis/ bronchitis 28 0 23 0
  UTIà 13 1 7 0
Nervous System Disorders
  Dysgeusia 26 0 4 0
  Dizziness 20 0 15 1
Metabolism and Nutrition Disorders
  Decreased appetite 20 0 10 0
Respiratory, Thoracic and Mediastinal Disorders
  Dyspneaè 15 0 6 0
* Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.
Includes abdominal pain, abdominal pain lower, abdominal pain upper, abdominal distension, abdominal discomfort, and abdominal tenderness.
Includes colitis, diarrhea, and gastroenteritis.
§ Includes stomatitis, aphthous ulcer; and mouth ulceration.
Includes asthenia, fatigue, lethargy, and malaise.
# Includes neutropenia, and febrile neutropenia.
Þ Includes leukopenia, and white blood cell count decreased.
? Includes platelet count decreased, and thrombocytopenia.
à Includes urosepsis, urinary tract infection, urinary tract pain, and pyuria.
è Includes dyspnea, and dyspnea exertional.

In addition, the adverse reactions observed in SOLO-1 that occurred in <10% of patients receiving Lynparza were increased blood creatinine (8%), lymphopenia (6%), hypersensitivity (2%), dermatitis (1%), and increased mean cell volume (0.4%).

Table 3 - Laboratory Abnormalities Reported in ≥25% of Patients in SOLO-1

Laboratory Parameter* Lynparza tablets
n=260
Placebo
n=130
Grades 1-4
(%)
Grades 3-4
(%)
Grades 1-4
(%)
Grades 3-4
(%)
Decrease in hemoglobin 87 19 63 2
Increase in mean corpuscular volume 87 - 43 -
Decrease in leukocytes 70 7 52 1
Decrease in lymphocytes 67 14 29 5
Decrease in absolute neutrophil count 51 9 38 6
Decrease in platelets 35 1 20 2
Increase in serum creatinine 34 0 18 0
* Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.

First-Line Maintenance Treatment Of HRD-Positive Advanced Ovarian Cancer In Combination With Bevacizumab

PAOLA-1

The safety of Lynparza in combination with bevacizumab for the maintenance treatment of patients with advanced ovarian cancer following first-line treatment containing platinum-based chemotherapy and bevacizumab was investigated in PAOLA-1 [see Clinical Studies]. This study was a placebo-controlled, double-blind study in which 802 patients received either Lynparza 300 mg BID in combination with bevacizumab (n=535) or placebo in combination with bevacizumab (n=267) until disease progression or unacceptable toxicity. The median duration of treatment with Lynparza was 17.3 months and 11 months for bevacizumab post-randomization on the Lynparza/bevacizumab arm.

Fatal adverse reactions occurred in 1 patient due to concurrent pneumonia and aplastic anemia. Serious adverse reactions occurred in 31% of patients who received Lynparza/bevacizumab. Serious adverse reactions in >5% of patients included hypertension (19%) and anemia (17%).

Dose interruptions due to an adverse reaction of any grade occurred in 54% of patients receiving Lynparza/bevacizumab and dose reductions due to an adverse reaction occurred in 41% of patients who received Lynparza/bevacizumab.

The most frequent adverse reactions leading to dose interruption in the Lynparza/bevacizumab arm were anemia (21%), nausea (7%), vomiting (3%), and fatigue (3%), and the most frequent adverse reactions leading to reduction in the Lynparza/bevacizumab arm were anemia (19%), nausea (7%), and fatigue (4%).

Discontinuation due to adverse reactions occurred in 20% of patients receiving Lynparza/bevacizumab. Specific adverse reactions that most frequently led to discontinuation in patients treated with Lynparza/bevacizumab were anemia (4%) and nausea (3%).

Tables 4 and 5 summarize adverse reactions and laboratory abnormalities in PAOLA-1, respectively.

Table 4 - Adverse Reactions* Occurring in ≥10% of Patients Treated with Lynparza/bevacizumab in PAOLA-1 and at ≥5% Frequency Compared to the Placebo/bevacizumab Arm

Adverse Reactions Lynparza/ bevacizumab
n=535
Placebo/ bevacizumab
n=267
Grades 1-4
(%)
Grades 3-4
(%)
Grades 1-4
(%)
Grades 3-4
(%)
General Disorders and Administration Site Conditions
  Fatigue (including asthenia) 53 5 32 1.5
Gastrointestinal Disorders
  Nausea 53 2.4 22 0.7
  Vomiting 22 1.7 11 1.9
Blood and Lymphatic Disorders
  Anemia 41 17 10 0.4
  Lymphopenia§ 24 7 9 1.1
  Leukopenia? 18 1.9 10 1.5
* Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.
Includes asthenia, and fatigue.
Includes anemia, anemia macrocytic, erythropenia, haematocrit decreased, haemoglobin decreased, normochromic anemia, normochromic normocytic anemia, normocytic anemia, and red blood cell count decreased. Includes B-lymphocyte count decreased, lymphocyte count decreased, lymphopenia, and T-lymphocyte count decreased.
§ Includes B-lymphocyte count decreased, lymphocyte count decreased, lymphopenia, and T-lymphocyte count decreased.
? Includes leukopenia, and white blood cell count decreased.

The most common adverse reactions (≥ 10%) for patients receiving Lynparza/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia, vomiting (22%), diarrhea (18%), neutropenia (18%), leukopenia (18%), urinary tract infection (15%), and headache (14%).

The adverse reactions that occurred in <10% of patients receiving Lynparza/bevacizumab were dysgeusia (8%), dyspnea (8%), stomatitis (5%), dyspepsia (4.3%), erythema (3%), dizziness (2.6%), and hypersensitivity (1.7%).

In addition, venous thromboembolic events occurred more commonly in patients receiving Lynparza/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).

Table 5 - Laboratory Abnormalities Reported in ≥25% of Patients in PAOLA-1*

Laboratory Parameter Lynparza/ bevacizumab
n=535
Placebo/ bevacizumab
n=267
Grades 1-4
(%)
Grades 3-4
(%)
Grades 1-4
(%)
Grades 3-4
(%)
Decrease in hemoglobin 79 13 55 0.4
Decrease in lymphocytes 63 10 42 3.0
Increase in serum creatinine 61 0.4 36 0.4
Decrease in leukocytes 59 3.4 45 2.2
Decrease in absolute neutrophil count 35 7 30 3.7
Decrease in platelets 35 2.4 28 0.4
* Reported within 30 days of the last dose.
Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.

Maintenance Treatment Of Recurrent Ovarian Cancer

SOLO-2

The safety of Lynparza for the maintenance treatment of patients with platinum sensitive gBRCAm ovarian cancer was investigated in SOLO-2 [see Clinical Studies]. Patients received Lynparza tablets 300 mg orally twice daily (n=195) or placebo (n=99) until disease progression or unacceptable toxicity. The median duration of study treatment was 19.4 months for patients who received Lynparza and 5.6 months for patients who received placebo.

Among patients who received Lynparza, dose interruptions due to an adverse reaction of any grade occurred in 45% and dose reductions due to an adverse reaction occurred in 27%. The most frequent adverse reactions leading to dose interruption or reduction of Lynparza were anemia (22%), neutropenia (9%), and fatigue/asthenia (8%). Discontinuation due to an adverse reaction occurred in 11% of patients receiving Lynparza.

Tables 6 and 7 summarize adverse reactions and laboratory abnormalities in SOLO-2.

Table 6 - Adverse Reactions* in SOLO-2 (≥20% of Patients Who Received Lynparza)

Adverse Reaction Lynparza tablets
n=195
Placebo
n=99
Grades 1-4
(%)
Grades 3-4
(%)
Grades 1-4
(%)
Grades 3-4
(%)
Gastrointestinal Disorders
  Nausea 76 3 33 0
  Vomiting 37 3 19 1
  Diarrhea 33 2 22 0
  Stomatitis 20 1 16 0
General Disorders and Administration Site Conditions
  Fatigue including asthenia 66 4 39 2
Blood and Lymphatic Disorders
  Anemia 44 20 9 2
Infections and Infestations
   Nasopharyngitis/URI/sinusitis/ rhinitis/influenza 36 0 29 0
Musculoskeletal and Connective Tissue Disorders
  Arthralgia/myalgia 30 0 28 0
Nervous System Disorders
  Dysgeusia 27 0 7 0
  Headache 26 1 14 0
Metabolism and Nutrition Disorders
  Decreased appetite 22 0 11 0
* Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.
Represents grouped term consisting of abscess oral, aphthous ulcer, gingival abscess, gingival disorder, gingival pain, gingivitis, mouth ulceration, mucosal infection, mucosal inflammation, oral candidiasis, oral discomfort, oral herpes, oral infection, oral mucosal erythema, oral pain, oropharyngeal discomfort, and oropharyngeal pain.
Represents grouped term consisting of anemia, hematocrit decreased, hemoglobin decreased, iron deficiency, mean cell volume increased and red blood cell count decreased.

In addition, the adverse reactions observed in SOLO-2 that occurred in <20% of patients receiving Lynparza were neutropenia (19%), cough (18%), leukopenia (16%), hypomagnesemia (14%), thrombocytopenia (14%), dizziness (13%), dyspepsia (11%), increased creatinine (11%), edema (8%), rash (6%), and lymphopenia (1%).

Table 7 - Laboratory Abnormalities Reported in ≥25% of Patients in SOLO-2

Laboratory Parameter* Lynparza tablets
n=195
Placebo
n=99
Grades 1-4
(%)
Grades 3-4
(%)
Grades 1-4
(%)
Grades 3-4
(%)
Increase in mean corpuscular volume 89 - 52 -
Decrease in hemoglobin 83 17 69 0
Decrease in leukocytes 69 5 48 1
Decrease in lymphocytes 67 11 37 1
Decrease in absolute neutrophil count 51 7 34 3
Increase in serum creatinine 44 0 29 0
Decrease in platelets 42 2 22 1
* Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.
Represents the proportion of subjects whose mean corpuscular volume was > upper limit of normal (ULN).

Study 19

The safety of Lynparza as maintenance monotherapy was evaluated in patients with platinum sensitive ovarian cancer who had received 2 or more previous platinum containing regimens in Study 19 [see Clinical Studies]. Patients received Lynparza capsules 400 mg orally twice daily (n=136) or placebo (n=128). At the time of final analysis, the median duration of exposure was 8.7 months in patients who received Lynparza and 4.6 months in patients who received placebo.

Adverse reactions led to dose interruptions in 35% of patients receiving Lynparza; dose reductions in 26% and discontinuation in 6% of patients receiving Lynparza.

Tables 8 and 9 summarize adverse reactions and laboratory abnormalities in Study 19.

Table 8 - Adverse Reactions* in Study 19 (≥20% of Patients Who Received Lynparza)

Adverse Reaction Lynparza capsules
n=136
Placebo
n=128
Grades 1-4
(%)
Grades 3-4
(%)
Grades 1-4
(%)
Grades 3-4
(%)
Gastrointestinal Disorders
  Nausea 71 2 36 0
  Vomiting 35 2 14 1
  Diarrhea 28 2 25 2
  Constipation 22 1 12 0
  Dyspepsia 20 0 9 0
General Disorders and Administration Site Conditions
  Fatigue (including asthenia) 63 9 46 3
Blood and Lymphatic Disorders
  Anemia 23 7 7 1
Infections and Infestations
  Respiratory tract infection 22 2 11 0
Metabolism and Nutrition Disorders
  Decreased appetite 21 0 13 0
Nervous System Disorders
  Headache 21 0 13 1
* Graded according to NCI CTCAE v4.0.
Represents grouped terms of related terms that reflect the medical concept of the adverse reaction.

In addition, the adverse reactions in Study 19 that occurred in <20% of patients receiving Lynparza were dysgeusia (16%), dizziness (15%), dyspnea (13%), pyrexia (10%), stomatitis (9%), edema (9%), increase in creatinine (7%), neutropenia (5%), thrombocytopenia (4%), leukopenia (2%), and lymphopenia (1%).

Table 9 - Laboratory Abnormalities Reported in ≥25% of Patients in Study 19

Laboratory Parameter* Lynparza capsules
n=136
Placebo
n=129
Grades 1-4
(%)
Grades 3-4
(%)
Grades 1-4
(%)
Grades 3-4
(%)
Decrease in hemoglobin 82 8 58 1
Increase in mean corpuscular volume 82 - 51 -
Decrease in leukocytes 58 4 37 2
Decrease in lymphocytes 52 10 32 3
Decrease in absolute neutrophil count 47 7 40 2
Increase in serum creatinine 45 0 14 0
Decrease in platelets 36 4 18 0
* Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.
Represents the proportion of subjects whose mean corpuscular volume was > ULN.

Advanced Germline BRCA-Mutated Ovarian Cancer After 3 Or More Lines Of Chemotherapy

Pooled Data

The safety of Lynparza was investigated in 223 patients (pooled from 6 studies) with gBRCAm advanced ovarian cancer who had received 3 or more prior lines of chemotherapy [see Clinical Studies]. Patients received Lynparza capsules 400 mg orally twice daily until disease progression or unacceptable tolerability. The median exposure to Lynparza in these patients was 5.2 months.

There were 8 (4%) patients with adverse reactions leading to death, two were attributed to acute leukemia, and one each was attributed to COPD, cerebrovascular accident, intestinal perforation, pulmonary embolism, sepsis, and suture rupture. Adverse reactions led to dose interruption in 40% of patients, dose reduction in 4%, and discontinuation in 7%.

Tables 10 and 11 summarize the adverse reactions and laboratory abnormalities from the pooled studies.

Table 10 - Adverse Reactions Reported in Pooled Data (≥20% of Patients Who Received Lynparza)

Adverse Reaction Lynparza capsules
n=223
Grades 1-4
(%)
Grades 3-4
(%)
General Disorders
  Fatigue/asthenia 66 8
Gastrointestinal Disorders
  Nausea 64 3
  Vomiting 43 4
  Diarrhea 31 1
  Dyspepsia 25 0
  Decreased appetite 22 1
Blood and Lymphatic Disorders
  Anemia 34 18
Infections and Infestations
  Nasopharyngitis/URI 26 0
Musculoskeletal and Connective Tissue Disorders
  Arthralgia/musculoskeletal pain 21 0
  Myalgia 22 0

Table 11 - Laboratory Abnormalities Reported in ≥25% of Patients in Pooled Data

Laboratory Parameter* Lynparza capsules
n=223
Grades 1-4
(%)
Grades 3-4
(%)
Decrease in hemoglobin 90 15
Mean corpuscular volume elevation 57 -
Decrease in lymphocytes 56 17
Decrease in platelets 30 3
Increase in creatinine 30 2
Decrease in absolute neutrophil count 25 7
* Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.

The following adverse reactions and laboratory abnormalities have been identified in ≥10 to <20% of the 223 patients receiving Lynparza and not included in the table: cough (16%), constipation (16%), dysgeusia (16%), headache (15%), peripheral edema (14%), back pain (14%), urinary tract infection (14%), dyspnea (13%), and dizziness (11%).

The following adverse reactions and laboratory abnormalities have been identified in <10% of the 223 patients receiving Lynparza and not included in the table: leukopenia (9%), pyrexia (8%), peripheral neuropathy (5%), hypomagnesemia (5%), rash (5%), stomatitis (4%), and venous thrombosis (including pulmonary embolism) (1%).

Germline BRCA-Mutated HER2-Negative Metastatic Breast Cancer

OlympiAD

The safety of Lynparza was evaluated in gBRCAm patients with HER2-negative metastatic breast cancer who had previously received up to two lines of chemotherapy for the treatment of metastatic disease in OlympiAD [see Clinical Studies]. Patients received either Lynparza tablets 300 mg orally twice daily (n=205) or a chemotherapy (capecitabine, eribulin, or vinorelbine) of the healthcare provider’s choice (n=91) until disease progression or unacceptable toxicity. The median duration of study treatment was 8.2 months in patients who received Lynparza and 3.4 months in patients who received chemotherapy.

Among patients who received Lynparza, dose interruptions due to an adverse reaction of any grade occurred in 35% and dose reductions due to an adverse reaction occurred in 25%. Discontinuation due to an adverse reaction occurred in 5% of patients receiving Lynparza.

Tables 12 and 13 summarize the adverse reactions and laboratory abnormalities in OlympiAD.

Table 12 - Adverse Reactions* in OlympiAD (≥20% of Patients Who Received Lynparza)

Adverse Reaction Lynparza tablets
n=205
Chemotherapy
n=91
Grades 1-4
(%)
Grades 3-4
(%)
Grades 1-4
(%)
Grades 3-4
(%)
Gastrointestinal Disorders
  Nausea 58 0 35 1
  Vomiting 30 0 15 1
  Diarrhea 21 1 22 0
Blood and Lymphatic Disorders
  Anemia 40 16 26 4
  Neutropenia 27 9 50 26
  Leukopenia§ 25 5 31 13
General Disorders and Administration Site Conditions
  Fatigue (including asthenia) 37 4 36 1
Infections and Infestations
  Respiratory tract infection? 27 1 22 0
Nervous System Disorders
  Headache 20 1 15 2
* Graded according to NCI CTCAE v4.0.
Represents grouped terms consisting of anemia (anemia erythropenia, hematocrit decreased, hemoglobin decreased and red blood cell count decreased).
Represents grouped terms consisting of neutropenia (febrile neutropenia, granulocyte count decreased, granulocytopenia, neutropenia, neutropenic infection, neutropenic sepsis, and neutrophil count decreased).
§ Represents grouped terms consisting of leukopenia (leukopenia and white blood cell count decreased).
? Represents grouped terms consisting of bronchitis, influenza, lower respiratory tract infection, nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis, sinusitis, upper respiratory tract infection, and upper respiratory tract infection bacterial.

In addition, adverse reactions in OlympiAD that occurred in <20% of patients receiving Lynparza were cough (18%), decreased appetite (16%), thrombocytopenia (11%), dysgeusia (9%), lymphopenia (8%), dyspepsia (8%), dizziness (7%), stomatitis (7%), upper abdominal pain (7%), rash (5%), increase in serum creatinine (3%), and dermatitis (1%).

Table 13 - Laboratory Abnormalities Reported in ≥25% of Patients in OlympiAD

Laboratory Parameter* Lynparza tablets
n= 205
Chemotherapy
n= 91
Grades 1-4
(%)
Grades 3-4
(%)
Grades 1-4
(%)
Grades 3-4
(%)
Decrease in hemoglobin 82 17 66 3
Decrease in lymphocytes 73 21 63 3
Decrease in leukocytes 71 8 70 23
Increase in mean corpuscular volume 71 - 33 -
Decrease in absolute neutrophil count 46 11 65 38
Decrease in platelets 33 3 28 0
* Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.
Represents the proportion of subjects whose mean corpuscular volume was > ULN.

First-Line Maintenance Treatment Of Germline BRCA-Mutated Metastatic Pancreatic Adenocarcinoma

POLO

The safety of Lynparza as maintenance treatment of germline BRCA-mutated metastatic pancreatic adenocarcinoma following first-line treatment with platinum-based chemotherapy was evaluated in POLO [see Clinical Studies]. Patients received Lynparza tablets 300 mg orally twice daily (n=90) or placebo (n=61) until disease progression or unacceptable toxicity. Among patients receiving Lynparza, 34% were exposed for 6 months or longer and 25% were exposed for greater than one year.

Among patients who received Lynparza, dosage interruptions due to an adverse reaction of any grade occurred in 35% and dosage reductions due to an adverse reaction occurred in 17%. The most frequent adverse reactions leading to dosage interruption or reduction in patients who received Lynparza were anemia (11%), vomiting (5%), abdominal pain (4%), asthenia (3%), and fatigue (2%). Discontinuation due to adverse reactions occurred in 6% of patients receiving Lynparza. The most frequent adverse reaction that led to discontinuation of Lynparza was fatigue (2.2%).

Tables 14 and 15 summarize the adverse reactions and laboratory abnormalities in patients in POLO.

Table 14 - Adverse Reactions* in POLO (Occurring in ≥10% of Patients who Received Lynparza)

Adverse Reaction Lynparza tablets
(n=91)
Placebo
(n=60)
All Grades
( %)
Grades 3 – 4
(%)
All Grades
(%)
Grades 3 – 4
(%)
General Disorders and Administration Site Conditions
  Fatigue 60 5 35 2
Gastrointestinal Disorders
  Nausea 45 0 23 2
  Abdominal pain^ 34 2 37 5
  Diarrhea 29 0 15 0
  Constipation 23 0 10 0
  Vomiting 20 1 15 2
  Stomatitis§ 10 0 5 0
Blood and Lymphatic System Disorders
  Anemia 27 11 17 3
  Thrombocytopenia? 14 3 7 0
  Neutropenia 12 4 8 3
Metabolism and Nutrition Disorders
  Decreased appetite 25 3 7 0
Musculoskeletal and Connective Tissue Disorders
  Back pain 19 0 17 2
  Arthralgia 15 1 10 0
Skin and Subcutaneous Tissue Disorder
  Rash# 15 0 5 0
Respiratory, Thoracic and Mediastinal Disorders
  Dyspnea** 13 0 5 2
Infections and Infestations
  Nasopharyngitis 12 0 3 0
Nervous System Disorders
  Dysgeusia 11 0 5 0
* Graded according to NCI CTCAE, version 4.0
This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.
Includes asthenia and fatigue
^ Includes abdominal pain, abdominal pain upper, abdominal pain lower
§ Includes stomatitis and mouth ulceration
? Includes platelets count decreased and thrombocytopenia
Includes neutropenia, febrile neutropenia and neutrophil count decreased
# Includes rash erythematous, rash macular and rash maculo-papular **Includes dyspnea and dyspnea exertional

In addition, the adverse reactions observed in POLO that occurred in <10% of patients receiving Lynparza were cough (9%), abdominal pain upper (7%), blood creatinine increased (7%), dizziness (7%), headache (7%), dyspepsia (5%), leukopenia (5%), hypersensitivity (2%), and lymphopenia (2%).

Table 15 - Laboratory Abnormalities Reported in ≥25% of Patients in POLO

Laboratory Parameter* Lynparza tablets
n=91
Placebo
n=60
Grades 1-4
(%)
Grades 3-4
(%)
Grades 1-4
(%)
Grades 3-4
(%)
Increase in serum creatinine 99 2 85 0
Decrease in hemoglobin 86 11 65 0
Increase in mean corpuscular volume 71 - 30 -
Decrease in lymphocytes 61 9 27 0
Decrease in platelets 56 2 39 0
Decrease in leukocytes 50 3 23 0
Decrease in absolute neutrophil count 25 3 10 0
* Patients were allowed to enter POLO with hemoglobin ≥9 g/dL (CTCAE Grade 2) and other laboratory values of CTCAE Grade 1.
This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.
Represents the proportion of subjects whose mean corpuscular volume was > ULN.

HRR Gene-Mutated Metastatic Castration-Resistant Prostate Cancer

PROfound

The safety of Lynparza as monotherapy was evaluated in patients with mCRPC and HRR gene mutations who have progressed following prior treatment with enzalutamide or abiraterone in PROfound [see Clinical Studies]. This study was a randomized, open-label, multi-center study in which 386 patients received either Lynparza tablets 300 mg orally twice daily (n=256) or investigator’s choice of enzalutamide or abiraterone acetate (n=130) until disease progression or unacceptable toxicity. Among patients receiving Lynparza, 62% were exposed for 6 months or longer and 20% were exposed for greater than one year.

Fatal adverse reactions occurred in 4% of patients treated with Lynparza. These included pneumonia (1.2%), cardiopulmonary failure (0.4%), aspiration pneumonia (0.4%), intestinal diverticulum (0.4%), septic shock (0.4%), Budd-Chiari Syndrome (0.4%), sudden death (0.4%), and acute cardiac failure (0.4%).

Serious adverse reactions occurred in 36% of patients receiving Lynparza. The most frequent serious adverse reactions (≥2%) were anemia (9%), pneumonia (4%), pulmonary embolism (2%), fatigue/asthenia (2%), and urinary tract infection (2%).

Dose interruptions due to an adverse reaction of any grade occurred in 45% of patients receiving Lynparza; dose reductions due to an adverse reaction occurred in 22% of Lynparza patients. The most frequent adverse reactions leading to dose interruption of Lynparza were anemia (25%) and thrombocytopenia (6%) and the most frequent adverse reaction leading to reduction of Lynparza was anemia (16%). Discontinuation due to adverse reactions occurred in 18% of Lynparza. The adverse reaction that most frequently led to discontinuation of Lynparza was anemia (7%).

Tables 16 and 17 summarize the adverse reactions and laboratory abnormalities, respectively, in patients in PROfound.

Table 16 - Adverse Reactions* Reported in ≥10% of Patients in PROfound

Adverse Reactions Lynparza tablets
n=256
Enzalutamide or abiraterone
n=130
Grades 1-4
(%)
Grades 3-4
(%)
Grades 1-4
(%)
Grades 3-4
(%)
Blood and lymphatic disorders
  Anemia 46 21 15 5
  Thrombocytopenia 12 4 3 0
Gastrointestinal disorders
  Nausea 41 1 19 0
  Diarrhea 21 1 7 0
  Vomiting 18 2 12 1
General disorders and administration site conditions
  Fatigue (including asthenia) 41 3 32 5
Metabolism and nutrition disorders
  Decreased appetite 30 1 18 1
Respiratory, thoracic, and mediastinal disorders
  Cough 11 0 2 0
  Dyspnea 10 2 3 0
* Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03
Includes anemia and hemoglobin decreased
Includes platelet count decreased and thrombocytopenia

In addition, adverse reactions of clinical relevance in PROfound that occurred in <10% of patients receiving Lynparza were neutropenia (9%), venous thromboembolic events (7%), dizziness (7%), dysgeusia (7%), dyspepsia (7%), headache (6%), pneumonia (5%), stomatitis (5%), rash (4%), blood creatinine increase (4%), pneumonitis (2%), upper abdominal pain (2%), and hypersensitivity (1%).

Table 17 - Laboratory Abnormalities Reported in ≥25% of Patients in PROfound

Laboratory Parameter* Lynparza tablets
n= 256
Enzalutamide or abiraterone
n=130
Grades 1-4
n= 247
(%)
Grades 3-4
n=247
(%)
Grades 1-4
n=124
(%)
Grades 3-4
n=124
(%)
Decrease in hemoglobin 242 (98) 33 (13) 91 (73) 5 (4)
Decrease in lymphocytes 154 (62) 57 (23) 42 (34) 16 (13)
Decrease in leukocytes 130 (53) 9 (4) 26 (21) 0
Decrease in absolute neutrophil count 83 (34) 8 (3) 11 (9) 0
* Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Lynparza. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: Hypersensitivity (rash/dermatitis/angioedema).

DRUG INTERACTIONS

Use With Anticancer Agents

Clinical studies of Lynparza with other myelosuppressive anticancer agents, including DNA damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

Effect Of Other Drugs On Lynparza

Strong And Moderate CYP3A Inhibitors

Coadministration of CYP3A inhibitors can increase olaparib concentrations, which may increase the risk for adverse reactions [see CLINICAL PHARMACOLOGY]. Avoid coadministration of strong or moderate CYP3A inhibitors. If the strong or moderate inhibitor must be coadministered, reduce the dose of Lynparza [see DOSAGE AND ADMINISTRATION].

Strong And Moderate CYP3A Inducers

Concomitant use with a strong or moderate CYP3A inducer decreased olaparib exposure, which may reduce Lynparza efficacy [see CLINICAL PHARMACOLOGY]. Avoid coadministration of strong or moderate CYP3A inducers.

Read the entire FDA prescribing information for Lynparza (Olaparib Capsules for Oral Administration)

© Lynparza Patient Information is supplied by Cerner Multum, Inc. and Lynparza Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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