NOVA Safety

Most Hematologic ARs Occurred During the
First 3 Months of Therapy¹

NOVA: Hematologic ARs reported in ≥10% of patients receiving ZEJULA²

Chart showing the incidence of hematologic adverse reactions in greater than or equal to 10% of patients receiving ZEJULA (niraparib)

The rate of grade ≥3 thrombocytopenia after cycle 3 was 2% in patients receiving ZEJULA.³

Abnormal laboratory findings (grades 1-4) in ≥25% of patients receiving ZEJULA²

Decrease in hemoglobin (85%), decrease in platelet count (72%), decrease in white blood cell count (66%), decrease in absolute neutrophil count (53%), increase in AST (36%), and increase in ALT (28%)

Discontinuation Due to Hematologic ARs Was Uncommon²

Table depicting percentage rate of discontinuation of ZEJULA (niraparib) due to various hematologic adverse reactions

Hematologic ARs generally occurred within the first 3 treatment cycles; after dose adjustment on the basis of an individual adverse event profile, the incidence of grade 3/4 thrombocytopenia, neutropenia, or fatigue was infrequent beyond cycle 3³
1 patient (<1%) in the ZEJULA arm experienced febrile neutropenia⁴

Low rates of treatment discontinuation were observed due to ARs²

In the same clinical trial, 15% of the overall population discontinued treatment due to ARs²

Thrombocytopenia Was Typically Transient With Dose Modification^3,4

Platelet levels decreased initially but showed stabilization after cycle 3 with appropriate dose modification³

The median time to onset of grade 3/4 thrombocytopenia was 23 days in the ZEJULA treatment arm⁴
Most grade 3/4 thrombocytopenia events were transient with dose interruption or dose reduction. The median duration was 10 days⁴

Change in platelet levels from baseline over time³

Graph showing change in platelet levels from baseline over time

No clinically significant bleeding events (grade ≥3) were associated with thrombocytopenia.⁵

All bleeding events associated with thrombocytopenia were grade 1/2; 1 patient had grade 3 petechiae and hematoma concurrent with a serious adverse event of pancytopenia⁵

Incidence of grade 3/4 thrombocytopenia in the ZEJULA arm of the NOVA trial; treatment months 1-5⁴

Graph showing incidence of grade 3/4 thrombocytopenia in the ZEJULA (niraparib) arm of the NOVA trial

Monitoring complete blood counts, blood pressure, and heart rate will help identify the need to dose modify²

Knowledge card with information about monitoring the blood count, blood pressure and heart rate for ZEJULA (niraparib) patients

*Monitor periodically. Schedule provided as an example.

Non-Hematologic Adverse Reactions

The Side Effect Profile of ZEJULA Is Well Characterized²

Adverse reactions (ARs) reported in ≥10% of patients receiving ZEJULA²

CTCAE, Common Terminology Criteria for Adverse Events, version 4.02.

ALT, alanine aminotransferase; AST, aspartate aminotransferase.

Side effects were manageable with dose interruption and modification.

ARs led to dose reduction or interruption in 69% of patients, most frequently from thrombocytopenia (41%) and anemia (20%)²
No increase in all-grade diarrhea was observed with ZEJULA vs placebo⁵
No on-treatment deaths were reported during the study⁵

ALT, alanine aminotransferase; AR, adverse reaction; AST, aspartate aminotransferase; SE, standard error.

quadra safety

See safety results for
QUADRA

View Adverse Reactions

Dose
Modifications

See recommendations for dose adjustments

Review Dosing

References: 1. Berek JS, Matulonis UA, Peen U, et al. Safety and dose modification for patients receiving niraparib. Ann Oncol. 2018;29(8):1784-1792. 2. ZEJULA (niraparib). Prescribing Information. GlaxoSmithKline; 2021. 3. Mirza MR, Monk BJ, Herrstedt J, et al; for the ENGOT-OV16/NOVA Investigators. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer [supplementary index]. N Engl J Med. 2016;375(22):‍2154-2164. 4. Data on file, GlaxoSmithKline. 5. Mirza MR, Monk BJ, Herrstedt J, et al; for the ENGOT-OV16/NOVA Investigators. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375(22):‍2154-2164.

Indications

Important Safety Information

Indication and Important Safety Info

ZEJULA is for the maintenance treatment of women with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer in a complete or partial response to first-line platinum-based chemotherapy

ZEJULA is indicated:

for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy
for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy

ZEJULA is indicated:

for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy
for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy
for the treatment of adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:
- a deleterious or suspected deleterious BRCA mutation, or
- genomic instability and who have progressed more than six months after response to the last platinum-based chemotherapy

Select patients for therapy based on an FDA-approved companion diagnostic for ZEJULA.

Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including some fatal cases, was reported in 15 patients (0.8%) out of 1785 patients treated with ZEJULA monotherapy in clinical trials. The duration of therapy in patients who developed secondary MDS/cancer therapy-related AML varied from 0.5 months to 4.9 years. These patients had received prior chemotherapy with platinum agents and/or other DNA-damaging agents including radiotherapy. Discontinue ZEJULA if MDS/AML is confirmed.

Important Safety Information

Hematologic adverse reactions (thrombocytopenia, anemia, neutropenia, and/or pancytopenia) have been reported in patients receiving ZEJULA. The overall incidence of Grade ≥3 thrombocytopenia, anemia, and neutropenia were reported, respectively, in 39%, 31%, and 21% of patients receiving ZEJULA in PRIMA; 29%, 25%, and 20% of patients receiving ZEJULA in NOVA; and 28%, 27%, and 13% of patients receiving ZEJULA in QUADRA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 4%, 2%, and 2% of patients in PRIMA; 3%, 1%, and 2% of patients in NOVA; and 4%, 2%, and 1% of patients in QUADRA. In patients who were administered a starting dose of ZEJULA based on baseline weight or platelet count in PRIMA, Grade ≥3 thrombocytopenia, anemia, and neutropenia were reported, respectively, in 22%, 23%, and 15% of patients receiving ZEJULA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 3%, 3%, and 2% of patients. Do not start ZEJULA until patients have recovered from hematological toxicity caused by prior chemotherapy (≤Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months, and periodically thereafter. If hematological toxicities do not resolve within 28 days following interruption, discontinue ZEJULA, and refer the patient to a hematologist for further investigations.

Hypertension and hypertensive crisis have been reported in patients receiving ZEJULA. Grade 3-4 hypertension occurred in 6% of patients receiving ZEJULA vs 1% of patients receiving placebo in PRIMA, with no reported discontinuations. Grade 3-4 hypertension occurred in 9% of patients receiving ZEJULA vs 2% of patients receiving placebo in NOVA, with discontinuation occurring in <1% of patients. Grade 3-4 hypertension occurred in 5% of ZEJULA-treated patients in QUADRA, with discontinuation occurring in <0.2% of patients. Monitor blood pressure and heart rate at least weekly for the first two months, then monthly for the first year, and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Manage hypertension with antihypertensive medications and adjustment of the ZEJULA dose if necessary.

Posterior reversible encephalopathy syndrome (PRES) occurred in 0.1% of 2,165 patients treated with ZEJULA in clinical trials and has also been described in postmarketing reports. Monitor all patients for signs and symptoms of PRES, which include seizure, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension. Diagnosis requires confirmation by brain imaging. If suspected, promptly discontinue ZEJULA and administer appropriate treatment. The safety of reinitiating ZEJULA is unknown.

Embryo-fetal toxicity and lactation: Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months after receiving their final dose of ZEJULA. Because of the potential for serious adverse reactions from ZEJULA in breastfed infants, advise lactating women to not breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose.

Allergic reactions to FD&C Yellow No. 5 (tartrazine): ZEJULA capsules contain FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

First-line Maintenance Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of all patients who received ZEJULA in PRIMA were thrombocytopenia (66%), anemia (64%), nausea (57%), fatigue (51%), neutropenia (42%), constipation (40%), musculoskeletal pain (39%), leukopenia (28%), headache (26%), insomnia (25%), vomiting (22%), dyspnea (22%), decreased appetite (19%), dizziness (19%), cough (18%), hypertension (18%), AST/ALT elevation (14%), and acute kidney injury (12%).

Common lab abnormalities (Grades 1-4) in ≥25% of all patients who received ZEJULA in PRIMA included: decreased hemoglobin (87%), decreased platelets (74%), decreased leukocytes (71%), increased glucose (66%), decreased neutrophils (66%), decreased lymphocytes (51%), increased alkaline phosphatase (46%), increased creatinine (40%), decreased magnesium (36%), increased AST (35%) and increased ALT (29%).

Maintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received ZEJULA in NOVA were nausea (74%), thrombocytopenia (61%), fatigue/asthenia (57%), anemia (50%), constipation (40%), vomiting (34%), neutropenia (30%), insomnia (27%), headache (26%), decreased appetite (25%), nasopharyngitis (23%), rash (21%), hypertension (20%), dyspnea (20%), mucositis/stomatitis (20%), dizziness (18%), back pain (18%), dyspepsia (18%), leukopenia (17%), cough (16%), urinary tract infection (13%), anxiety (11%), dry mouth (10%), AST/ALT elevation (10%), dysgeusia (10%), palpitations (10%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients who received ZEJULA in NOVA included: decrease in hemoglobin (85%), decrease in platelet count (72%), decrease in white blood cell count (66%), decrease in absolute neutrophil count (53%), increase in AST (36%), and increase in ALT (28%).

Treatment of Advanced HRD+ Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received ZEJULA in QUADRA were nausea (67%), fatigue (56%), thrombocytopenia (52%), anemia (51%), vomiting (44%), constipation (36%), abdominal pain (34%), musculoskeletal pain (29%), decreased appetite (27%), dyspnea (22%), insomnia (21%), neutropenia (20%), headache (19%), diarrhea (17%), acute kidney injury (17%), urinary tract infection (15%), hypertension (14%), cough (13%), dizziness (11%), AST/ALT elevation (11%), blood alkaline phosphatase increased (11%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients who received ZEJULA in QUADRA included: decreased hemoglobin (83%), increased glucose (66%), decreased platelets (60%), decreased lymphocytes (57%), decreased leukocytes (53%), decreased magnesium (46%), increased alkaline phosphatase (40%), increased gamma glutamyl transferase (40%), increased creatinine (36%), decreased sodium (34%), decreased neutrophils (34%), increased aspartate aminotransferase (29%), and decreased albumin (27%).

Please see accompanying Prescribing Information.

To report SUSPECTED ADVERSE REACTIONS, contact GSK at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

If your patients need help paying for their medicines or to learn about other patient access and reimbursement services, visit TogetherWithGSKOncology.com or call 1-844-4-GSK-ONC (1-844-447-5662)

Trademarks are property of their respective owners.

This is my caption

NOVA Safety

Most Hematologic ARs Occurred During the First 3 Months of Therapy1

Discontinuation Due to Hematologic ARs Was Uncommon2

Thrombocytopenia Was Typically Transient With Dose Modification3,4

Non-Hematologic Adverse Reactions

Most Hematologic ARs Occurred During the
First 3 Months of Therapy¹

Discontinuation Due to Hematologic ARs Was Uncommon²

Thrombocytopenia Was Typically Transient With Dose Modification^3,4