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Efficacy

PRIMA Study Design - A Phase 3 Trial in Advanced Ovarian Cancer1,2

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

PRIMA study design infographic



In PRIMA, HRd status was determined using the FDA-approved Myriad myChoice® CDx as either tBRCAm and/or GIS+ (GIS ≥42).1,3

  • a Patients were stratified based on neoadjuvant chemotherapy administered (yes or no), best response to 1L platinum therapy (CR or PR) and homologous recombination (HR) status (deficient [HR-deficient], proficient [HR-proficient], or not determined).1,2
  • b Patients in PRIMA received a starting dose of either 200 mg or 300 mg based on their baseline body weight or platelet count (n=169), or a fixed starting dose of 300 mg daily (n=315) regardless of body weight or platelet count.1-3

PRIMA enrolled a broad range of patients, including patients with poor prognoses who were at higher risk of progression1,2,4-7

Of patients in the overall population (N=733):

35 percent of patients icon

35%

had stage IV disease1,2
67 percent of patients icon

67%

had received neoadjuvant chemotherapy1,2
84 percent of patients icon

84%

had residual disease after primary debulking surgery4,c

Placebo: 8.2 Months1,2

MEDIAN PFS IN OVERALL POPULATION
 

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

 

c Stage III and IV disease with visible residual tumor (>0 cm) after primary debulking surgery.4

 

The PRIMA population may be reflective of your clinical practice8

ZEJULA is the only once-daily oral PARP inhibitor monotherapy available for HRd patients.1,9,10

PFS in HRd Population

More than doubled median PFS vs placebo in HRd patients1,2

PFS in the HRd population (n=373)1,2,d

PFS in the HRd population line graph

e Censored subjects are indicated by circles.

d At the time of primary analysis.

Consistent efficacy observed across exploratory HRd subgroups2,3,11,f

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

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

PFS in Overall Population

ZEJULA may mean more time living progression-free1,2

Significantly longer median PFS vs placebo1,2,g
 

PFS in the overall population (N=733)

PFS in the overall population line graph

h Censored subjects are indicated by circles.

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

PFS benefit was observed across exploratory patient subgroups vs placebo2,f

Exploratory efficacy in PRIMA chart

I If test results were inconclusive or the test was not done, tumors were considered HRnd.2

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

PRIMA Long-term PFS

HRd Long-term PFS

More than doubled 4-year PFS rates observed with ZEJULA in HRd patients vs placebo12

Exploratory ad hoc analysisj

3.5-year median follow-up of investigator-assessed PFS in the HRd population (n=373)12,j

PFS HRd population long term analysis

k Censored subjects are indicated by circles.

j Interpret results with caution.

  • Not powered to detect a statistically significant treatment effect
  • 4-year PFS rates estimated from Kaplan-Meier curve, with median follow-up time of 3.5 years12
  • The probability of patients in the HRd population to be alive and progression-free at 4 years was 38% in the ZEJULA arm vs 17% in the placebo arm12
  • With 3.5-year median follow-up, overall survival data remain immature at 41.2% for the overall population12

ZEJULA was associated with long-term PFS benefits for patients with HRd ovarian cancer12

Overall Population Long-term PFS

Continued confidence with ZEJULA: Durable PFS benefit observed consistent with primary analysis1,2,12

Exploratory ad hoc analysisl

3.5-year median follow-up of investigator-assessed PFS in the HRd population (n=373)12,l

PFS overall population long term analysis
m Censored subjects are indicated by circles.
l Interpret results with caution.
  • Not powered to detect a statistically significant treatment effect
  • 4-year PFS rates estimated from Kaplan-Meier curve, with median follow-up time of 3.5 years12
  • The probability of patients in the HRd population to be alive and progression-free at 4 years was 38% in the ZEJULA arm vs 17% in the placebo arm12
  • With 3.5-year median follow-up, overall survival data remain immature at 41.2% for the overall population12

Reduction in risk of progression or death remained consistent with the primary analysis1,2,12

With ZEJULA, durable outcomes were observed in PRIMA long-term data4

VIEW ZEJULA SAFETY DATA

1L = first-line; BRCA = breast cancer susceptibility gene; BRCAm = BRCA-mutated; BRCAwt = BRCA wild type; CI = confidence interval; CR = complete response; FIGO = International Federation of Gynecology and Obstetrics; GIS = genomic instability score; HR = hazard ratio; HRd = homologous recombination deficient; HRnd = homologous recombination status not determined; HRp = homologous recombination proficient; mPFS = median PFS; PARP = poly (ADP-ribose) polymerase; PFS = progression-free survival; PR = partial response; tBRCAm = tumor BRCA-mutated.

Indication & Important Safety Info

Indication

Important Safety Information

Indication

ZEJULA (niraparib) 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

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, 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. 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 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.

 

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 tablets.

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) Tablets. Prescribing Information. GSK; 2023.

  2. González-Martín A, Pothuri B, Vergote I, et al. N Engl J Med. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962

  3. González-Martín A, Pothuri B, Vergote I, et al. [supplementary appendix]. N Engl J Med. 2019;381(25):1-42. doi:10.1056/NEJMoa1910962

  4. Data on File, GSK.

  5. Horowitz NS, Miller A, Rungruang B, et al. J Clin Oncol. 2015;33(8):937-943. doi:10.1200/JCO.2014.56.3106

  6. Chang S-J, Hodeib M, Chang J, Bristow RE. Gynecol Oncol. 2013;130(3):493-498. doi:10.1016/j.ygyno.2013.05.040

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

  8. Rodrigues M, Joly F, Ray-Coquard I, et al. Poster presented at: European Society for Medical Oncology Congress; September 16-21, 2021; virtual.

  9. Lynparza (olaparib). Prescribing Information. AstraZeneca Pharmaceuticals LP; 2023.

  10. Rubraca (rucaparib). Prescribing Information. Clovis Oncology, Inc; 2023.

  11. Monk BJ, Han S, Pothuri B, et al. Presented at: Society of Gynecologic Oncology Annual Meeting on Women's Cancer Webinar Series; March 28-31, 2020.

  12. González-Martín A, Pothuri B, Vergote I, et al. Eur J Cancer. 2023;189:112908. doi:10.1016/j.ejca.2023.04.024

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