FOR 1L MAINTENANCE OF ADULT PATIENTS WITH PLATINUM-RESPONSIVE ADVANCED OVARIAN CANCER¹

ZEJULA is the only 1X daily oral PARP inhibitor
monotherapy.
ZEJULA delivered 2X the median PFS vs placebo in
HRd PATIENTS.^1-4

Study Design

The PRIMA trial assessed ZEJULA as 1L maintenance in patients with advanced ovarian cancer in response to platinum-based chemotherapy, regardless of biomarker status^1,2

PRIMA was a randomized, double-blind, placebo-controlled phase 3 trial examining the efficacy and safety of ZEJULA in patients with newly diagnosed advanced ovarian cancer.^1,2

In PRIMA, HRd status was determined using the FDA-approved Myriad™ myChoice CDx as either tBRCA+ and/or GIS+ (GIS ≥42).^1,5

Patients were stratified based on neoadjuvant chemotherapy administered (yes or no), best response to first-line platinum therapy (CR or PR), and homologous recombination (HR) status (deficient [HR-deficient], proficient [HR-proficient], or not determined).¹

Patients in PRIMA received an individualized starting dose of either 200 mg or 300 mg based on their baseline body weight or platelet count (n=258), or a fixed starting dose of 300 mg daily (n=475) regardless of body weight or platelet count.¹

PRIMA enrolled a broad range of patients, including patients with poor prognoses^1,2,6-10:

Of patients in the overall population:

HAD Residual Disease^10‡
AFTER PRIMARY DEBULKING SURGERY

HAD Stage IV Disease¹

HAD RECEIVED
Neoadjuvant Chemotherapy^1,2

Placebo: 8.2 Months¹
MEDIAN PFS IN OVERALL POPULATION

72% of patients on placebo estimated to have progressed or died within 2 years after diagnosis²

Stage III and IV disease with visible residual tumor (>0 cm) after primary debulking surgery.¹⁰

primary efficacy

Primary Efficacy
Overall Population
Primary Efficacy
HRd Population

ZEJULA significantly improved PFS in newly diagnosed patients who responded to platinum-based chemotherapy, regardless of biomarker status^1,2

PFS in the Overall Population (N=733)

Graph showing PFS in overall population with 38% reduction in risk of disease progression or death.

The overall population consisted of^1||:

Overall population for PRIMA included: HRd/BRCAm, HRd/BRCAwt, HRp

Censored subjects are indicated by circles.

Patients with HRnd (n=111) were included in the overall population.²

In the HRd population, ZEJULA doubled median PFS compared with placebo^1,2

PFS in the HRd Population (n=373, 51% of overall study population)

Graph showing PFS in HRd population with 57% reduction in risk of disease progression or death.

60% of patients in the HRd population were BRCAm²

Censored subjects are indicated by circles.

exploratory efficacy

A reduction in the risk of disease progression or death was observed with ZEJULA compared with placebo across multiple patient subgroups^1,2

These prespecified subgroup analyses are exploratory in nature and were not powered to detect a statistically significant treatment effect; therefore, results should be interpreted with caution.^1,2

Chart showing patient subgroups, hazard ratio for disease progression or death, and median PFS.

At the time of the PFS analysis, limited overall survival data were available with 11% deaths in the overall population.¹

Exploratory Efficacy BRCAm
Exploratory Efficacy HRd BRCAwt

60% reduction in the risk of disease progression or death compared with placebo was observed in a prespecified exploratory analysis of the BRCAm subgroup^2,3,10

This analysis is exploratory in nature and was not powered to detect a statistically significant treatment effect; therefore, results should be interpreted with caution.

PFS in the BRCAm Population (n=223)²

Graph showing PFS observed in HRd BRCAwt population with 60% reduction in risk of disease progression or death.

The efficacy with ZEJULA was observed to be consistent in HRd subgroups, regardless of BRCA status^2,5,11

Censored subjects are indicated by circles.²

Figure adapted from Monk BJ, et al. 2020.¹¹

50% reduction in the risk of disease progression or death compared with placebo was observed in a prespecified exploratory analysis of the HRd BRCAwt subgroup^2,3,10

This analysis is exploratory in nature and was not powered to detect a statistically significant treatment effect; therefore, results should be interpreted with caution.

PFS in the HRd BRCAwt Population (n=150)²

Graph showing PFS observed in BRCAm population with 50% reduction in risk of disease progression or death.

The efficacy with ZEJULA was observed to be consistent in HRd subgroups, regardless of BRCA status^2,5,11

Censored subjects are indicated by circles.²

Figure adapted from Monk BJ, et al. 2020.¹¹

Among the subgroup of patients with HRp (n=249)²

HR, 0.68 (95% CI, 0.49-0.94)

Among the subgroup of patients with HRnd (n=111)^2#

HR, 0.85 (95% CI, 0.51-1.43)

^#If test results were inconclusive or the test was not done, tumors were considered as homologous recombination status not determined (HRnd).⁵

quality of life

In an exploratory analysis, health-related quality of life was maintained with ZEJULA and comparable to placebo^2,5

This analysis is exploratory in nature and does not control for type 1 error; elements more distal to disease and treatment-related symptoms may be influenced by multiple nondrug factors.

FOSI in the Overall Population

Graph showing FOSI Adjusted Health Utility Index Score

FOSI is a validated 8-item measure of symptom response to treatment, including lack of energy, vomiting, pain, nausea, stomach swelling, worsening condition, quality of life as assessed by the patient, and cramps in the stomach area.⁵

Values displayed in the chart above are adjusted means; a higher score indicates fewer symptoms.

Continue the PRIMA story

View PRIMA Safety

Indication

Important Safety Information

Indication and Important Safety Info

ZEJULA (niraparib) capsules 100 mg and tablets 100 mg/200 mg/300 mg are indicated:

for first-line 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

ZEJULA (niraparib) capsules 100 mg and tablets 100 mg/200 mg/300 mg are indicated:

for first-line 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

ZEJULA (niraparib) capsules 100 mg and tablets 100 mg/200 mg/300 mg are indicated:

for first-line 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

Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including cases with a fatal outcome, have been reported in patients who received ZEJULA. In PRIMA, MDS/AML occurred in 6 out of 484 (1.2%) patients treated with ZEJULA, and in 3 out of 244 (1.2%) patients treated with placebo. The duration of therapy with ZEJULA in patients who developed secondary MDS/cancer therapy-related AML varied from 3.7 months to 2.5 years. All patients who developed secondary MDS/cancer therapy-related AML had received previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

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. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 4%, 2%, and 2% of patients in PRIMA. 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. 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 not to breastfeed during treatment with ZEJULA and for 1 month after receiving the last 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%).

Please see accompanying Prescribing Information for ZEJULA capsules and tablets.

1L = first-line; BRCA = breast cancer susceptibility gene; BRCA+ = BRCA-mutated; BRCA− = not BRCA-mutated; CI = confidence interval; CR = complete response; FOSI = Functional Assessment of Cancer Therapy-Ovarian Symptoms Index; GIS = genomic instability score; HR = hazard ratio; HRd = homologous recombination deficient; HRp = homologous recombination proficient; PARP = poly (ADP-ribose) polymerase; PFS = progression-free survival; PR = partial response; SE = standard error; tBRCA+ = tumor BRCA-mutated.

References: 1. ZEJULA (niraparib). Prescribing Information. GlaxoSmithKline; 2022. 2. González-Martín A, Pothuri B, Vergote I, et al; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019;381(25):1-42. doi:10.1056/NEJMoa1910962 3. Lynparza (olaparib). Prescribing Information. AstraZeneca Pharmaceuticals LP; 2022. 4. Rubraca (rucaparib). Prescribing Information. Clovis Oncology, Inc; 2022. 5. González-Martín A, Pothuri B, Vergote I, et al; for the PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in patients with newly diagnosed advanced ovarian cancer [supplementary appendix]. N Engl J Med. 2019;381(25):1-42. doi:10.1056/NEJMoa1910962 6. Howlader N, Noone AM, Krapcho M, et al (eds). SEER Cancer Statistics Review. 1975-2016. Bethesda, MD: National Cancer Institute. https://seer.cancer.gov/csr/1975_2016/, based on November 2020 SEER data submission, posted to the SEER website, April 2021. Accessed July 2, 2021. 7. Horowitz NS, Miller A, Rungruang B, et al Does aggressive surgery improve outcomes? Interaction between preoperative disease burden and complex surgery in patients with advanced-stage ovarian cancer: an analysis of GOG 182. J Clin Oncol. 2015;33(8):937-943. 8. Chang S-J, Hodeib M, Chang J, Bristow RE. Survival impact of complete cytoreduction to no gross residual disease for advanced-stage ovarian cancer: a meta-analysis. Gynecol Oncol. 2013;130(3):493-498. doi:10.1016/j.ygyno.2013.05.040 9. Davis A, Tinker AV, Friedlander M. “Platinum resistant” ovarian cancer: what is it, who to treat and how to measure benefit? Gynecol Oncol. 2014;133(3):624-631. doi:10.1016/j.ygyno.2014.02.038 10. Data on file, GlaxoSmithKline. 11. Monk BJ, Han S, Pothuri B, et al. Efficacy of niraparib therapy in patients with newly diagnosed advanced ovarian cancer by BRCA and homologous recombination status: PRIMA/ENGOT-OV26/GOG-3012 study. Presented at: Society of Gynecologic Oncology Annual Meeting on Women's Cancer Webinar Series; March 28-31, 2020.

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

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This is my caption

ZEJULA is the only 1X daily oral PARP inhibitor monotherapy. ZEJULA delivered 2X the median PFS vs placebo in HRd PATIENTS.1-4

ZEJULA is the only 1X daily oral PARP inhibitor
monotherapy.
ZEJULA delivered 2X the median PFS vs placebo in
HRd PATIENTS.^1-4