Maintenance Treatment of Recurrent Ovarian Cancer

NOVA

  • Study Design

    The Only Phase 3 Trial of a PARP Inhibitor to Isolate and Evaluate Efficacy in the gBRCAmut and in the Difficult-to-Treat Non-gBRCAmut Cohorts1-3

    Visual showing NOVA trial design of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer following CR or PR to second-line or later platinum-based chemotherapy and progression-free survival (PFS).
    Visual showing NOVA trial design of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer following CR or PR to second-line or later platinum-based chemotherapy and progression-free survival (PFS).
    • Progression-free survival (PFS) was measured from time of randomization to time of disease progression or death1

    *In the non-gBRCAmut cohort, women whose tumors had no BRCA mutation and women whose tumors were homologous recombination deficiency negative (HRDneg, also called homologous recombinant proficient, or HRp) comprised the majority of patients. This cohort included patients whose tumors were sBRCAmut or BRCAwt. Approximately 13% of women in the non-gBRCAmut cohort had tumors that were known to be sBRCAmut.6

    Randomization occurred within 8 weeks of the last dose of platinum-based therapy and was stratified by time to progression after the penultimate platinum therapy (6 to <12 months and ≥12 months), use of bevacizumab in conjunction with the penultimate or last platinum regimen (yes vs no), and best response during the last platinum regimen (CR and PR). Patients continued to receive ZEJULA or placebo until disease progression, unacceptable toxicity, death, withdrawal of consent, or loss to follow-up, whichever came first.1,4

    CT or MRI was performed at baseline and every 8 weeks through cycle 14, then every 12 weeks until treatment discontinuation. PFS was determined by central independent assessment per RECIST v1.1 or by more conservative measures of clinical signs and symptoms and increasing CA-125.1,4

    §Additional diagnostic tests included histology/cytology, ultrasound, endoscopy, and PET.4,5

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    NOVA Patient Population Included Women With and Without BRCAmut Tumors1,6,7

    Visual showing NOVA trial design of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who were in CR or PR.
    Visual showing NOVA trial design of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who were in CR or PR.

    ||In the non-gBRCAmut cohort, women whose tumors had no BRCA mutation and women whose tumors were homologous recombination deficiency negative (HRDneg) comprised the majority of patients. Approximately 13% of women in the non-gBRCAmut cohort had tumors that were known to be sBRCAmut.6

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    In NOVA, Patient Demographics Were Well-Balanced Across Treatment Arms and Representative of Women Seen in Clinical Practice1,4,7

    Visual showing NOVA patient demographics
    Visual showing NOVA patient demographics
    • Of the 26% of patients treated with ZEJULA who received prior bevacizumab in conjunction with the penultimate or last platinum regimen, 16% received ZEJULA as switch maintenance1,4,5

    BRCA, breast cancer susceptibility gene; BRCAmut, BRCA-mutated; BRCAwt, BRCA wild type; CA-125, cancer antigen 125; CR, complete response; CT, computed tomography; gBRCAmut, germline BRCA-mutated; HRD, homologous recombination deficiency; HRDneg, homologous recombination deficiency negative; HRDpos, HRD positive; MRI, magnetic resonance imaging; non-gBRCAmut, not germline BRCA-mutated; PARP, poly (ADP-ribose) polymerase; PET, positron emission tomography; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria In Solid Tumors; sBRCAmut, somatic BRCA-mutated.

  • Primary Efficacy: gBRCAmut

    In the gBRCAmut Cohort, the Median PFS Was Nearly 4x Longer Than Placebo (N=203)1,4,8

    PFS in the gBRCAmut cohort5

    Graph showing PFS in gBRCAmut cohort.
    Graph showing PFS in gBRCAmut cohort.

    *Censored subjects are indicated by closed circles.

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    An Exploratory Analysis of NOVA Suggested That ZEJULA Provided More Time Without Disease Progression Compared With Placebo, Independent of Baseline Patient Characteristics1,4,5

    This analysis is exploratory in nature; it does not control for type 1 error and was not powered to determine treatment effect in any subgroup.1,4,5

    Similar magnitude of benefit seen within key demographic and prognostic subgroups1,4,9

    Visual showing key demographic and prognostic subgroups for gBRCAmut efficacy in NOVA trial.

    BRCA, breast cancer susceptibility gene; CI, confidence interval; CR, complete response; gBRCAmut, germline BRCA-mutated; HR, hazard ratio; PFS, progression-free survival; PR, partial response.

  • Primary Efficacy: non-gBRCAmut

    In the Non-gBRCAmut Cohort, Median PFS With ZEJULA Was More Than 2x Longer Than With Placebo1,4,8

    PFS in the non-gBRCAmut cohort1,5,7

    Graph showing PFS in the non-gBRCAmut cohort.
    Graph showing PFS in the non-gBRCAmut cohort.

    *Censored subjects are indicated by open circles.

      Includes 13% sBRCA patients.

    • BRCAwt tumors are historically difficult to treat and are associated with poorer outcomes10,11
    • In the non-gBRCAmut cohort, approximately 13.4% of women were known to be sBRCAmut1,6

    Continued Platinum Eligibility Was Assessed in an Exploratory Analysis5

    55% more non-gBRCAmut women receiving ZEJULA (niraparib) remained platinum eligible compared with women receiving placebo.
    55% more non-gBRCAmut women receiving ZEJULA (niraparib) remained platinum eligible compared with women receiving placebo.

    In an exploratory analysis of patients in the NOVA trial, continued platinum eligibility was observed in 73% of non-gBRCAmut patients receiving ZEJULA and 47% of patients receiving placebo

    This analysis is exploratory in nature; it does not control for type 1 error and is not powered to determine treatment effect.5

    Includes 13% sBRCA+ patients.6 

    Analysis of platinum eligibility derived from NOVA trial dataset.6

    Platinum eligibility was defined by a platinum-free interval of ≥6 months.12 

    In an Exploratory Analysis, Improved Median PFS Was Observed in Patients With BRCAwt Tumors Who Received ZEJULA Compared to Placebo1,6

    This subgroup analysis is exploratory in nature; it does not control for type 1 error and is not powered to determine treatment effect in any subgroup.8,9

    VIEW DATA BY:

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    PFS in the BRCA wild-type, HRDpos subpopulation9

    Graph showing PFS in the BRCA wild-type, HRDpos subpopulation.
    Graph showing PFS in the BRCA wild-type, HRDpos subpopulation.

    §Censored subjects are indicated by closed circles.

    PFS in the BRCA wild-type, HRDneg subpopulation9

    Graph showing PFS in the BRCA wild-type, HRDneg subpopulation.
    Graph showing PFS in the BRCA wild-type, HRDneg subpopulation.

    §Censored subjects are indicated by closed circles.

    Continued Platinum Eligibility Was Assessed in an Exploratory Analysis5

    56% BRCAwt women receiving ZEJULA (niraparib) remained platinum eligible compared with women receiving placebo.
    56% BRCAwt women receiving ZEJULA (niraparib) remained platinum eligible compared with women receiving placebo.

    In an exploratory analysis of patients in the NOVA trial, continued platinum eligibility was observed in 70% of non-gBRCAmut patients receiving ZEJULA and 45% of patients receiving placebo.5,#

    This analysis is exploratory in nature; it does not control for type 1 error and is not powered to determine treatment effect.

    Includes 13% sBRCA+ patients.6 

    #Analysis of platinum eligibility derived from NOVA trial dataset.6

    Platinum eligibility was defined by a platinum-free interval of ≥6 months.12 

    A reduction in the risk of disease progression or death was observed with ZEJULA1,4,9 

    This analysis is exploratory in nature; it does not control for type 1 error and is not powered to determine treatment effect in any subgroup.1,4,9

    NOVA: Similar magnitude of benefit within key demographic and prognostic subgroups1

    Visual showing key demographic and prognostic subgroups for non-gBRCAmut efficacy in NOVA trial.

    BRCA, breast cancer susceptibility gene; BRCAneg, BRCA negative; BRCAwt, BRCA wild type; CI, confidence interval; CR, complete response; gBRCAmut, germline BRCA-mutated; HR, hazard ratio; HRD, homologous recombination deficiency; HRDneg, HRD negative; HRDpos, HRD positive; non-gBRCAmut, not germline BRCA-mutated; PFS, progression-free survival; PR, partial response; sBRCA, somatic BRCA; sBRCAmut, somatic BRCA-mutated.

  • Exploratory Analysis: Tolerability and Quality-of-Life

    ZEJULA Showed Long-Term Tolerability After Dose Modification, Including Patients Receiving Treatment for >2 Years1,13

    A long-term safety analysis of the NOVA study assessed the incidence of TEAEs in patients receiving ZEJULA for up to 4 years. Of the initial 367 patients in the ZEJULA treatment group and 179 in the placebo treatment group, 18.8% and 5.6% of patients were included in the 2- to 4-year evaluation period, respectively.

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    An Exploratory Analysis of NOVA Suggested That ZEJULA Did Not Adversely Affect Quality of Life1,6

    Based on the FOSI test, patients who received ZEJULA as maintenance treatment reported quality-of-life scores comparable to placebo during their treatment1,6

    • Values displayed in the chart below are adjusted means; a higher score suggests fewer symptoms6
    • FOSI assesses pain, fatigue, nausea, vomiting, bloating and cramping in the stomach area, worry about the condition getting worse, and level of content with quality of life5
    • 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

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    FOSI outcomes in the gBRCAmut cohort6,9

    Graph showing FOSI outcomes in the gBRCAmut cohort.
    Graph showing FOSI outcomes in the gBRCAmut cohort.

    FOSI outcomes in the non-gBRCAmut cohort6,9

    Graph showing FOSI outcomes in the non-gBRCAmut cohort.
    Graph showing FOSI outcomes in the non-gBRCAmut cohort.
    • FOSI completion rates were high and similar in the 2 treatment groups: 75% to 97% in the ZEJULA group and 80% to 97% in the placebo group5
    • Patients were assessed at baseline, every 8 weeks for the first year, every 12 weeks thereafter during treatment, and then 6 to 10 weeks after treatment discontinuation5

    BRCA, breast cancer susceptibility gene; C, cycle; FOSI, Functional Assessment of Cancer Therapy-Ovarian Symptoms Index; gBRCAmut, germline BRCA-mutated; non-gBRCAmut, not germline BRCA-mutated; SE, standard error; TEAEs, treatment-emergent adverse events.

SAFETY DATA

Learn about the safety
and tolerability of ZEJULA

Dose
Modifications

See recommendations for dose adjustments