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Efficacy

ZEJULA: The Only FDA-approved PARP Inhibitor With Statistically Significant PFS Across HRD-positive Advanced Ovarian Cancer1-3,a,b

 

For patients with complete or partial response to first-line platinum-based chemotherapy1

aDefined by either a deleterious BRCA mutation, and/or genomic instability.1

bPRIMA: A double-blind, placebo-controlled phase 3 trial of patients with newly diagnosed advanced ovarian cancer who were randomized 2:1 to ZEJULA or placebo. PFS was the primary endpoint evaluated by BICR, per RECIST v1.1, in the primary analysis (13.8-month follow-up). Homologous recombination status was a stratification factor in PRIMA, and hierarchical testing was used to control for overall type 1 error. In the HRD-positive population (n = 373): mPFS with ZEJULA was 21.9 months (95% CI, 19.3-NE) vs 10.4 months (95% CI, 8.1-12.1) with placebo; 
HR, 0.43 (95% CI, 0.31-0.59, P<0.0001).1,4

PRIMA Study Design – First-line Maintenance Treatment for HRD-positive Advanced Ovarian Cancer

PRIMA was a double-blind, placebo-controlled trial in which patients (N=733) in complete or partial response to first-line platinum-based chemotherapy were randomized 2:1 to ZEJULA or matched placebo. Efficacy was evaluated in 373 patients in the HRD-positive population.1,4,5,c

PRIMA study design infographic

In PRIMA, exclusion criteria included patients with stage III disease who had complete cytoreduction (i.e., no visible residual disease) after primary debulking surgery and patients who had undergone more than two debulking surgeries for the study disease.6

In PRIMA, HRD status was determined using an investigational HRD assay. HRD-positive status included either tBRCAm or a GIS ≥42.1

cPatients were stratified based on neoadjuvant chemotherapy administered (yes vs. no), best response to 1L platinum therapy (CR vs. PR) and HRD status (positive vs. negative or not determined).1,4

dHRD-positive patients in PRIMA received a starting dose of either 200 mg or 300 mg based on their baseline body weight or platelet count (n=86), or a fixed starting dose of 300 mg daily (n=159) regardless of body weight or platelet count.1,4,7

PRIMA enrolled a broad range of patients, including patients with poor prognoses who were at higher risk of progression1,4,8-11:

Of patients in the HRD-positive population (n=373):

36 percent of patients icon

36%

had stage IV disease1

63 percent of patients icon

63%

had received neoadjuvant chemotherapy1

86 percent of patients icon

~86%

had residual disease after primary debulking surgery8,e

65% of patients on placebo estimated to have progressed or died within 2 years after diagnosis4

 

eStage III and IV disease with visible residual tumor (>0 cm) after primary debulking surgery.8

 

The PRIMA population may be reflective of your clinical practice12

ZEJULA is the only once-daily oral PARP inhibitor monotherapy available for patients with HRD-positive advanced ovarian cancer.1-3

Primary Analysis

The PRIMA trial met its primary endpoint: ZEJULA more than doubled median PFS vs placebo in the HRD-positive population1,4

Primary analysis

13.8-month median follow-up of PFS by BICR in the HRD-positive population (n=373)4

PFS in the HRd population line graph

fCensored subjects are indicated by circles.

Consistent efficacy observed across exploratory HRD-positive subgroups4,7,13,g

BRCAwt (n=150)

HR, 0.50

(95% CI, 0.31-0.83)

50% reduction in risk of progression or death

Median PFS of 19.6 months for ZEJULA vs 8.2 months with placebo

BRCAm (n=223)

HR, 0.40

(95% CI, 0.27-0.62)

60% reduction in risk of progression or death

Median PFS of 22.1 months for ZEJULA vs 10.9 months with placebo

gExploratory subgroup analysis, not powered to detect a statistically significant treatment effect. Interpret results with caution.

Final Analysis

5-year PFS rate in HRD-positive population

More than doubled 5-year PFS rates observed with ZEJULA in HRD-positive population vs placebo5

Exploratory ad hoc analysish

6.2-year median follow-up of investigator-assessed PFS in the HRD-positive population (n=373)5,h

Exploratory ad hoc analysis chart

hInterpret results with caution.

  • Not powered to detect a statistically significant treatment effect
  • 5-year PFS rates estimated from Kaplan-Meier curve, with median follow-up time of 6.2 years5
  • The probability of patients in the HRD-positive population to be alive and progression-free at 5 years was 35% in the ZEJULA arm vs 16% in the placebo arm5
    iCensored subjects are indicated by circles.

OS in HRD-positive population

Overall survival, a key secondary endpoint, was evaluated in the HRD-positive population after 185 events were observed1,5

  Events, n (%) Median OS
(95% CI)		 HR
(95% CI)
ZEJULA
 (n = 247)		 120 (48.6) 71.9 months
(55.5-NE)		 0.95
(0.71-1.29)
Placebo
 (n = 126)		 65 (51.6) 69.8 months
(51.6-NE)

In the control arm, PRIMA patients on placebo received nearly 3-fold higher subsequent PARP inhibitor treatment (48.4%) compared to patients in the ZEJULA arm (15.8%).14

ZEJULA was associated with long-term PFS benefits for patients with HRD-positive ovarian cancer5

SEE ZEJULA SAFETY DATA

1L = first-line; BICR = blinded independent central review; BRCA = breast cancer susceptibility gene; BRCAm = BRCA-mutated; BRCAwt = BRCA wild type; CI = confidence interval; CR = complete response; FDA = US Food and Drug Administration; GIS = genomic instability score; HR = hazard ratio; HRD = homologous recombination deficient; mPFS = median PFS; NE = not estimated; OS = overall survival; PARP = poly (ADP-ribose) polymerase; PFS = progression-free survival; PR = partial response; RECIST = Response Evaluation Criteria in Solid Tumors; tBRCAm = tumor BRCA-mutated.

INDICATION & IMPORTANT SAFETY INFORMATION

INDICATION

IMPORTANT SAFETY INFORMATION

INDICATION

ZEJULA (niraparib) is 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 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.

IMPORTANT SAFETY INFORMATION

Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including cases with a fatal outcome, have been reported in patients who received ZEJULA. In PRIMA, of patients within the HRD-positive population, MDS/AML occurred in 8 out of 245 (3.3%) patients treated with ZEJULA, and in 3 out of 125 (2.4%) patients treated with placebo with a follow-up of 6.1 years. The duration of therapy with ZEJULA in patients who developed secondary MDS/cancer therapy-related AML varied from 5.5 months to 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. For suspected MDS/AML or prolonged hematological toxicities, refer the patient to a hematologist for further evaluation. Discontinue ZEJULA if MDS/AML is confirmed.

 

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 cardiovascular effects 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.

 

First-line Maintenance Treatment of HRD-Positive Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of all patients who received ZEJULA in PRIMA were thrombocytopenia (66%), anemia (65%), nausea (62%), fatigue (52%), musculoskeletal pain (46%), neutropenia (43%), constipation (40%), leukopenia (29%), headache (27%), insomnia (25%), vomiting (23%), dyspnea (21%), decreased appetite (20%), dizziness (20%), cough (20%), hypertension (20%), AST/ALT elevation (14%), acute kidney injury (13%), and anxiety (12%).

 

Common lab abnormalities (Grades 1-4) in ≥25% of all patients who received ZEJULA in PRIMA included: decreased hemoglobin (85%), decreased leukocytes (72%), decreased platelets (71%), decreased neutrophils (64%), increased glucose (62%), decreased lymphocytes (55%), increased alkaline phosphatase (48%), increased creatinine (40%), decreased magnesium (39%), increased AST (35%), increased ALT (32%), and increased calcium (31%).

 

Please see the full Prescribing Information for ZEJULA.

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

References

  1. ZEJULA (niraparib). Prescribing information. GSK; 2025.

  2. Lynparza (olaparib). Prescribing information. AstraZeneca Pharmaceuticals LP; 2023.

  3. Rubraca (rucaparib). Prescribing information. pharmaand GmbH; 2024.

  4. González-Martín A et al. N Engl J Med. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962

  5. Monk BJ et al. Ann Oncol. 2024;35(11):981-992. doi:10.1016/j.annonc.2024.08.2241

  6. A study of niraparib (GSK3985771) maintenance treatment in participants with advanced ovarian cancer following response on front-line platinum-based chemotherapy. ClinicalTrials.gov identifier: NCT02655016. Updated October 2, 2024. Accessed April 29, 2025. https://clinicaltrials.gov/study/NCT02655016

  7. González-Martín A et al. N Engl J Med. 2019;381(25):1-42. doi:10.1056/NEJMoa1910962 

  8. Data on File, GSK.

  9. Horowitz NS et al. J Clin Oncol. 2015;33(8):937-943. doi:10.1200/JCO.2014.56.3106

  10. Chang S-J et al. Gynecol Oncol. 2013;130(3):493-498. doi:10.1016/j.ygyno.2013.05.040

  11. Davis A, Tinker AV, Friedlander M. Gynecol Oncol. 2014;133(3):624-631. doi:10.1016/j.ygyno.2014.02.038

  12. Rodrigues M et al. Poster presented at: European Society for Medical Oncology Congress; September 16-21, 2021; virtual.

  13. Monk BJ et al. Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer Webinar Series; March 28-31, 2020.

  14. Monk BJ et al. Ann Oncol. 2024;35(11):981-992. doi:10.1016/jannonc.2024.08.2241

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