DOSE MODIFICATIONS
Dose modifications due to adverse reactions in LYNPARZA pivotal trials
Advanced ovarian cancer (in combination)1-4
| PAOLA-1 | ||
|---|---|---|
LYNPARZA + bevacizumab (LYNPARZA component) (n=535) |
Placebo + bevacizumab (placebo component) (n=267) |
|
Discontinuations |
20% |
6% |
Reductions* |
41% |
7% |
Interruptions† |
54% |
24% |
| PAOLA-1 | |
|---|---|
LYNPARZA + bevacizumab (LYNPARZA component) (n=535) |
Placebo + bevacizumab (placebo component) (n=267) |
Discontinuations
|
|
| 20% | 6% |
Reductions*
|
|
| 41% | 7% |
Interruptions†
|
|
| 54% | 24% |
*In PAOLA-1, LYNPARZA dose reduction or discontinuation was considered after a patient resumed treatment after a dose interruption. In the case of dose reduction, the LYNPARZA dose was reduced to 250 mg BID. If further reduction was needed, then the dose could be reduced to 200 mg BID.
†For LYNPARZA, repeated dose interruptions in PAOLA-1 were allowed as required for a maximum of 4 weeks on each occasion.
8 out of 10 patients remained on LYNPARZA as prescribed in combination with bevacizumab without discontinuing due to ARs
In PAOLA-1: Anemia (4%) and nausea (3%) were reported to cause discontinuation rates ≥2%; all other ARs leading to discontinuation occurred with a frequency of 1% or below. Recorded ARs occurred during study treatment or up to 30 days after discontinuing the intervention.
Bevacizumab toxicity during PAOLA-1 was managed according to the Prescribing Information for bevacizumab, which could have included dose interruption, modification, or discontinuation. Please refer to the current version of the bevacizumab Prescribing Information for bevacizumab guidance. If LYNPARZA was temporarily interrupted for toxicity related to LYNPARZA, bevacizumab was continued unless the toxicity of LYNPARZA prevented patients from taking bevacizumab or increased the risk of bevacizumab toxicity. In this case, both treatments were interrupted until toxicity resolution (or NCI CTCAE Grade 1).
Advanced or recurrent ovarian cancer (as monotherapy)1,5-10
| SOLO-1 | SOLO-2 | |||
|---|---|---|---|---|
LYNPARZA (n=260) |
Placebo (n=130) |
LYNPARZA (n=260) |
Placebo (n=130) |
|
Discontinuations
|
12% |
2% |
11% |
2% |
Reductions*
|
28% |
3% |
27% |
3% |
Interruptions†
|
52% |
17% |
45% |
18% |
| SOLO-1 | |
|---|---|
LYNPARZA (n=260) |
Placebo (n=130) |
Discontinuations
|
|
| 12% | 2% |
Reductions*
|
|
| 28% | 3% |
Interruptions†
|
|
| 52% | 17% |
| SOLO-2 | |
LYNPARZA (n=260) |
Placebo (n=130) |
Discontinuations
|
|
| 11% | 2% |
Reductions*
|
|
| 27% | 3% |
Interruptions†
|
|
| 45% | 18% |
*In SOLO-1 and SOLO-2, LYNPARZA dose reduction or discontinuation was considered after a patient resumed treatment after a dose interruption. In the case of dose reduction, the LYNPARZA dose was reduced to 250 mg BID. If further reduction was needed, then the dose could be reduced to 200 mg BID.
†For LYNPARZA, repeated dose interruptions in SOLO-1 and SOLO-2 were allowed as required for a maximum of 14 days on each occasion.
~9 out of 10 patients remained on LYNPARZA without an AR-related discontinuation
~3 out of 4 patients remained on LYNPARZA without a dose reduction due to an AR
In SOLO-1: The most frequent ARs leading to dose interruption or reduction of LYNPARZA were anemia (23%), nausea (14%), and vomiting (10%). The most frequent ARs that led to discontinuation were fatigue (3.1%), anemia (2.3%), and nausea (2.3%).
In SOLO-2: The most frequent ARs leading to dose interruption or reduction of LYNPARZA were anemia (22%), neutropenia (9%), and fatigue/asthenia (8%).
Cross-trial comparisons should not be made.
Metastatic prostate cancer1,11,12
| PROpel | |||
|---|---|---|---|
LYNPARZA with abiraterone + prednisone or prednisolone (LYNPARZA component) (n=398) |
|||
Discontinuations
|
16% |
||
Reductions*
|
21% |
||
Interruptions†
|
48% |
||
| PROpel | |
|---|---|
LYNPARZA with abiraterone + prednisone or prednisolone (LYNPARZA component) (n=398) |
|
Discontinuations
|
|
| 16% | |
Reductions*
|
|
| 21% | |
Interruptions†
|
|
| 48% | |
*In PROpel, LYNPARZA dose reduction was considered after a patient resumed treatment after a dose interruption; the LYNPARZA dose was reduced to 250 mg BID. If further reduction was needed, then the dose could be reduced to 200 mg BID. If the reduced dose of 200 mg BID was not tolerated, no further dose reduction was allowed and LYNPARZA was discontinued.
†For LYNPARZA, repeated dose interruptions in PROpel were allowed as required for a maximum of 4 weeks on each occasion.
In PROpel, 84% of patients remained on LYNPARZA without discontinuing due to adverse reactions.
The most common (>2%) adverse reactions requiring dosage interruption of LYNPARZA were anemia (16%), COVID-19 (6%), fatigue (3.5%), nausea (2.8%), pulmonary embolism (2.3%), and diarrhea (2.3%); the most common (>2%) adverse reactions requiring dosage reductions of LYNPARZA were anemia (11%) and fatigue (2.5%). The most common adverse reactions that resulted in permanent discontinuation of LYNPARZA were anemia (4.3%) and pneumonia (1.5%).
Metastatic prostate cancer1,13,14
| PROfound | ||
|---|---|---|
LYNPARZA (n=256) |
Investigator's choice of enzalutamide or abiraterone (n=130) |
|
Discontinuations |
18% |
8% |
Reductions* |
22% |
4% |
Interruptions† |
45% |
18% |
| PROfound | |
|---|---|
LYNPARZA (n=256) |
Investigator's choice of enzalutamide or abiraterone (n=130) |
Discontinuations |
|
| 18% | 8% |
Reductions* |
|
| 22% | 4% |
Interruptions† |
|
| 45% | 18% |
*In PROfound, the LYNPARZA dose was reduced to 250 mg BID. If further reduction was needed, then the dose could be reduced to 200 mg BID. If the reduced dose of 200 mg BID was not tolerated, no further dose reduction was allowed and LYNPARZA was discontinued.
†For LYNPARZA, repeated dose interruptions in PROfound were allowed as required for a maximum of 4 weeks on each occasion.
In PROfound, 82% of patients remained on LYNPARZA without discontinuing due to adverse reactions.
In PROfound: The most frequent ARs leading to dose interruption of LYNPARZA were anemia (25%) and thrombocytopenia (6%), and the most frequent AR leading to reduction was anemia (16%). The AR that most frequently led to discontinuation was anemia (7%).
Early breast cancer1,15
| OlympiA | ||
|---|---|---|
LYNPARZA (n=911) |
||
Discontinuations
|
10% |
|
Reductions*
|
23% |
|
Interruptions†
|
31% |
|
| OlympiA | |
|---|---|
LYNPARZA (n=911) |
|
Discontinuations
|
|
| 10% | |
Reductions*
|
|
| 23% | |
Interruptions†
|
|
| 31% | |
*In OlympiA, the LYNPARZA dose was reduced to 250 mg BID. If further reduction was needed, then the dose could be reduced to 200 mg BID. If the reduced dose was not tolerated, no further dose reduction was allowed and LYNPARZA was discontinued.
†For LYNPARZA, dose interruptions in OlympiA were allowed for a maximum of 4 weeks. If the AR causing the dose interruption was not resolved at 4 weeks, LYNPARZA was discontinued.
~9 out of 10 patients remained on LYNPARZA without an AR-related discontinuation
In OlympiA: The most frequent ARs leading to dose interruption of LYNPARZA were anemia (11%), neutropenia (6%), nausea (5%), leukopenia (3.5%), fatigue (3%), and vomiting (2.9%) and the most frequent ARs leading to dose reduction of LYNPARZA were anemia (8%), nausea (4.7%), neutropenia (4.2%), fatigue (3.3%), leukopenia (1.8%), and vomiting (1.5%). The ARs that most frequently led to discontinuation of LYNPARZA were nausea (2%), anemia (1.8%), and fatigue (1.3%).
Metastatic breast cancer1,3,16
| OlympiAD | ||
|---|---|---|
LYNPARZA (n=205) |
Chemotherapy (n=91) |
|
Discontinuations
|
5% |
8% |
Reductions*
|
25% |
31% |
Interruptions†
|
35% |
28% |
| OlympiAD | |
|---|---|
LYNPARZA (n=205) |
Chemotherapy (n=91) |
Discontinuations
|
|
| 5% | 8% |
Reductions*
|
|
| 25% | 31% |
Interruptions†
|
|
| 35% | 28% |
*In OlympiAD, the LYNPARZA dose was reduced to 250 mg BID. If further reduction was needed, then the dose could be reduced to 200 mg BID. If the reduced dose of 200 mg BID was not tolerated, no further dose reduction was allowed and LYNPARZA was discontinued.
†For LYNPARZA, repeated dose interruptions in OlympiAD were allowed as required for a maximum of 4 weeks on each occasion.
~9 out of 10 patients remained on LYNPARZA without an AR-related discontinuation
~3 out of 4 patients remained on LYNPARZA without a dose reduction due to an AR
In OlympiAD: Patients received LYNPARZA or physician’s choice of chemotherapy (capecitabine, eribulin, or vinorelbine).
Metastatic pancreatic cancer1,17
| POLO | ||
|---|---|---|
LYNPARZA (n=90) |
||
Discontinuations
|
6% |
|
Reductions*
|
17% |
|
Interruptions†
|
35% |
|
| POLO | |
|---|---|
LYNPARZA (n=90) |
|
Discontinuations
|
|
| 6% | |
Reductions*
|
|
| 17% | |
Interruptions†
|
|
| 35% | |
*In POLO, the LYNPARZA dose was reduced to 250 mg BID. If further reduction was needed, then the dose could be reduced to 200 mg BID.
†For LYNPARZA, repeated dose interruptions in POLO were allowed as required for a maximum of 4 weeks on each occasion.
~9 out of 10 patients remained on LYNPARZA without AR-related discontinuation
In POLO: The most frequent ARs leading to dosage interruption or reduction in patients who received LYNPARZA were anemia (11%), vomiting (5%), abdominal pain (4%), asthenia (3%), and fatigue (2%). The most frequent AR that led to discontinuation was fatigue (2.2%).
See Important Safety Information, including Warnings and Precautions for MDS/AML, pneumonitis, venous thromboembolism, drug-induced liver injury and embryo-fetal toxicity below.
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INDICATIONS
LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:
First-Line Maintenance BRCAm
Advanced Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
First-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab
In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either:
- a deleterious or suspected deleterious BRCA mutation, and/or
- genomic instability
Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
Maintenance BRCA-mutated Recurrent Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer
For the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative, high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
gBRCAm, HER2-Negative Metastatic Breast Cancer
For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer
For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
BRCAm Metastatic Castration-Resistant Prostate Cancer in Combination with Abiraterone and Prednisone or Prednisolone
In combination with abiraterone and prednisone or prednisolone (abi/pred) for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC). Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
There are no contraindications for LYNPARZA.
WARNINGS AND PRECAUTIONS
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.2% of patients (26/2219) with various BRCAm, gBRCAm, HRR gene-mutated or HRD-positive cancers who received LYNPARZA in clinical studies as a single agent or as part of a combination regimen, consistent with the approved indications, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was approximately 2 years (range: <6 months to >4 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.
In SOLO-1, patients with newly diagnosed advanced BRCAm ovarian cancer, the incidence of MDS/AML was 1.9% (5/260) in patients who received LYNPARZA and 0.8% (1/130) in patients who received placebo based on an updated analysis. In PAOLA-1, of patients with newly diagnosed advanced ovarian cancer with HRD-positive status, the incidence of MDS/AML was 1.6% (4/255) in patients who received LYNPARZA and 2.3% (3/131) in the control arm.
In SOLO-2, patients with BRCAm platinum-sensitive relapsed ovarian cancer, the incidence of MDS/AML was 8% (15/195) in patients who received LYNPARZA and 4% (4/99) in patients who received placebo. The duration of LYNPARZA treatment prior to the diagnosis of MDS/AML ranged from 0.6 years to 4.5 years.
Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.
Pneumonitis: Including severe and fatal cases, has occurred in patients treated with LYNPARZA. In clinical studies, among patients who received LYNPARZA as a single agent or as part of a combination regimen, the incidence of pneumonitis, including fatal cases, was 1.0% (29/2851). If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and promptly assess the source of the symptoms. If pneumonitis is confirmed, discontinue LYNPARZA treatment and treat the patient appropriately.
Venous Thromboembolism (VTE): Including severe or fatal pulmonary embolism (PE), occurred in patients treated with LYNPARZA. In the combined data of two randomized, placebo-controlled clinical studies (PROfound and PROpel) in patients with metastatic castration-resistant prostate cancer (N=1180), VTE occurred in 8% of patients who received LYNPARZA, including pulmonary embolism in 6%. In the control arms, VTE occurred in 2.5%, including pulmonary embolism in 1.5%. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated.
Hepatotoxicity, including Drug-Induced Liver Injury (DILI): Hepatotoxicity, including severe and potentially fatal cases of DILI has occurred in patients treated with LYNPARZA. Evaluate bilirubin and transaminases at baseline and throughout treatment with LYNPARZA. For patients who develop abnormal liver tests after LYNPARZA, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold LYNPARZA. Upon confirmation of DILI, discontinue LYNPARZA.
Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. Verify pregnancy status in females of reproductive potential prior to initiating treatment.
Females
Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.
Males
Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.
ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer
Most common adverse reactions (all Grades) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary tract infection (13%), thrombocytopenia (11%), and stomatitis (11%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).
ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab
Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab and at a ≥5% frequency compared to placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%), and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%), and headache (14%).
In addition, venous thromboembolism occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%), and decrease in platelets (35%).
ADVERSE REACTIONS—Maintenance gBRCAm Recurrent Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/sinusitis/rhinitis/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: increase in mean corpuscular volume (89%), decrease in hemoglobin (83%), decrease in leukocytes (69%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), increase in serum creatinine (44%), and decrease in platelets (42%).
ADVERSE REACTIONS—Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: nausea (57%), fatigue (including asthenia) (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%), and stomatitis (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: decrease in lymphocytes (77%), increase in mean corpuscular volume (67%), decrease in hemoglobin (65%), decrease in leukocytes (64%), and decrease in absolute neutrophil count (39%).
ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer
Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).
ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic Pancreatic Adenocarcinoma
Most common adverse reactions (all Grades) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%).
ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA for PROfound were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).
ADVERSE REACTIONS—Metastatic Castration-Resistant Prostate Cancer in Combination with Abiraterone and Prednisone or Prednisolone
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA/abiraterone with a difference of ≥5% compared to placebo/abiraterone for PROpel were: anemia (48%), fatigue (including asthenia) (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia (14%), dizziness (14%), and abdominal pain (13%).
Most common laboratory abnormalities (Grades 1-4) in ≥20% of patients who received LYNPARZA/abiraterone for PROpel were: decrease in hemoglobin (97%), decrease in lymphocytes (70%), decrease in platelets (23%), and decrease in absolute neutrophil count (23%).
DRUG INTERACTIONS
Anticancer Agents: Clinical studies of LYNPARZA with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.
CYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.
CYP3A Inducers: Avoid coadministration of strong or moderate CYP3A inducers when using LYNPARZA.
USE IN SPECIFIC POPULATIONS
Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.
Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.
Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).
Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).
Please see complete Prescribing Information, including Medication Guide.
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See Important Safety Information, including Warnings and Precautions for MDS/AML, pneumonitis, venous thromboembolism, drug-induced liver injury and embryo-fetal toxicity below.
IMPORTANT SAFETY INFORMATION
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
There are no contraindications for LYNPARZA.
WARNINGS AND PRECAUTIONS
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.2% of patients (26/2219) with various BRCAm, gBRCAm, HRR gene-mutated or HRD-positive cancers who received LYNPARZA in clinical studies as a single agent or as part of a combination regimen, consistent with the approved indications, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was approximately 2 years (range: <6 months to >4 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.
In SOLO-1, patients with newly diagnosed advanced BRCAm ovarian cancer, the incidence of MDS/AML was 1.9% (5/260) in patients who received LYNPARZA and 0.8% (1/130) in patients who received placebo based on an updated analysis. In PAOLA-1, of patients with newly diagnosed advanced ovarian cancer with HRD-positive status, the incidence of MDS/AML was 1.6% (4/255) in patients who received LYNPARZA and 2.3% (3/131) in the control arm.
In SOLO-2, patients with BRCAm platinum-sensitive relapsed ovarian cancer, the incidence of MDS/AML was 8% (15/195) in patients who received LYNPARZA and 4% (4/99) in patients who received placebo. The duration of LYNPARZA treatment prior to the diagnosis of MDS/AML ranged from 0.6 years to 4.5 years.
Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.
Pneumonitis: Including severe and fatal cases, has occurred in patients treated with LYNPARZA. In clinical studies, among patients who received LYNPARZA as a single agent or as part of a combination regimen, the incidence of pneumonitis, including fatal cases, was 1.0% (29/2851). If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and promptly assess the source of the symptoms. If pneumonitis is confirmed, discontinue LYNPARZA treatment and treat the patient appropriately.
Venous Thromboembolism (VTE): Including severe or fatal pulmonary embolism (PE), occurred in patients treated with LYNPARZA. In the combined data of two randomized, placebo-controlled clinical studies (PROfound and PROpel) in patients with metastatic castration-resistant prostate cancer (N=1180), VTE occurred in 8% of patients who received LYNPARZA, including pulmonary embolism in 6%. In the control arms, VTE occurred in 2.5%, including pulmonary embolism in 1.5%. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated.
Hepatotoxicity, including Drug-Induced Liver Injury (DILI): Hepatotoxicity, including severe and potentially fatal cases of DILI has occurred in patients treated with LYNPARZA. Evaluate bilirubin and transaminases at baseline and throughout treatment with LYNPARZA. For patients who develop abnormal liver tests after LYNPARZA, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold LYNPARZA. Upon confirmation of DILI, discontinue LYNPARZA.
Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. Verify pregnancy status in females of reproductive potential prior to initiating treatment.
Females
Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.
Males
Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.
ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer
Most common adverse reactions (all Grades) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary tract infection (13%), thrombocytopenia (11%), and stomatitis (11%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).
ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab
Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab and at a ≥5% frequency compared to placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%), and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%), and headache (14%).
In addition, venous thromboembolism occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%), and decrease in platelets (35%).
ADVERSE REACTIONS—Maintenance gBRCAm Recurrent Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/sinusitis/rhinitis/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: increase in mean corpuscular volume (89%), decrease in hemoglobin (83%), decrease in leukocytes (69%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), increase in serum creatinine (44%), and decrease in platelets (42%).
ADVERSE REACTIONS—Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: nausea (57%), fatigue (including asthenia) (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%), and stomatitis (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: decrease in lymphocytes (77%), increase in mean corpuscular volume (67%), decrease in hemoglobin (65%), decrease in leukocytes (64%), and decrease in absolute neutrophil count (39%).
ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer
Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).
ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic Pancreatic Adenocarcinoma
Most common adverse reactions (all Grades) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%).
ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA for PROfound were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).
ADVERSE REACTIONS—Metastatic Castration-Resistant Prostate Cancer in Combination with Abiraterone and Prednisone or Prednisolone
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA/abiraterone with a difference of ≥5% compared to placebo/abiraterone for PROpel were: anemia (48%), fatigue (including asthenia) (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia (14%), dizziness (14%), and abdominal pain (13%).
Most common laboratory abnormalities (Grades 1-4) in ≥20% of patients who received LYNPARZA/abiraterone for PROpel were: decrease in hemoglobin (97%), decrease in lymphocytes (70%), decrease in platelets (23%), and decrease in absolute neutrophil count (23%).
DRUG INTERACTIONS
Anticancer Agents: Clinical studies of LYNPARZA with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.
CYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.
CYP3A Inducers: Avoid coadministration of strong or moderate CYP3A inducers when using LYNPARZA.
USE IN SPECIFIC POPULATIONS
Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.
Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.
Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).
Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).
Please see complete Prescribing Information, including Medication Guide.
You may report side effects related to AstraZeneca
products .
AR=adverse reaction; BID=twice daily; CTCAE=Common Terminology Criteria for Adverse Events; NCI=National Cancer Institute.
References:
LYNPARZA® (olaparib) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2025.
Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381(25):2416-2428.
Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. Protocol. N Engl J Med. 2019;381(25):2416-2428.
Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. Supplementary Appendix. N Engl J Med. 2019;381(25):2416-2428.
Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379(26):2495-2505.
Pujade-Lauraine E, Ledermann JA, Selle F, et al; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(9):1274-1284.
Friedlander M, Matulonis U, Gourley C, et al. Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy. Br J Cancer. 2018;119(9):1075-1085.
Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. Protocol. N Engl J Med. 2018;379(26):2495-2505.
Pujade-Lauraine E, Ledermann JA, Selle F, et al; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Protocol. Lancet Oncol. 2017;18(9):1274-1284.
Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. Protocol. N Engl J Med. 2012;366(15):1382-1392.
Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al; PROpel Investigators. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. NEJM Evid. Published online June 3, 2022. doi:10.1056/EVIDoa2200043
Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al; PROpel Investigators. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. Protocol. NEJM Evid. Published online June 3, 2022. doi:10.1056/EVIDoa2200043
de Bono J, Mateo J, Fizazi K, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. 2020;382(22):2091-2102.
de Bono J, Mateo J, Fizazi K, et al. Olaparib for metastatic castration-resistant prostate cancer. Protocol. N Engl J Med. 2020;382(22):2091-2102.
Tutt ANJ, Garber JE, Kaufman B, et al; OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. Protocol. N Engl J Med. 2021;384(25):2394-2405.
Robson M, Im S-A, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. Protocol. N Engl J Med. 2017;377(6):523-533.
Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. POLO Protocol. N Engl J Med. 2019;381(4):317-327.
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