MAINTENANCE THERAPY OF RECURRENT OVARIAN CANCER WITH ZEJULA

Efficacy Data From the NOVA Trial


Study Design

The only phase 3 trial of a PARP inhibitor to isolate and evaluate efficacy in the gBRCAm and in the difficult-to-treat non-gBRCAm 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-gBRCAm cohort, women whose tumors had no BRCA mutation and women whose tumors were homologous recombination deficiency negative (HRDneg, also called homologous recombination proficient, or HRp) comprised the majority of patients. This cohort included patients whose tumors were sBRCAm or BRCAwt. Approximately 13% of women in the  non-gBRCAm cohort had tumors that were known to be sBRCAm.5

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

  • Expand NOVA Patient Genetic Characteristics

    NOVA patient population included women with and without gBRCAm tumors1,5,6

    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-gBRCAm 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 gBRCAwt cohort had tumors that were known to be sBRCAm.5

In NOVA, patient demographics were well-balanced across treatment arms and representative of patients seen in clinical practice1,4,6

57-63


Median age across cohorts

~50%


Patients in PR to most recent platinum-based regimen

~40%


≥3 prior lines

~26%


Prior bevacizumab

7.6%


Measurable 
tumors >2 cm

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 maintenance1,4,6


primary efficacy

In the gBRCAm cohort, the median PFS was nearly 4x longer than placebo (N=203)1,4,7

PFS in the gBRCAm cohort1,4,7

Graph showing PFS in gBRCAm cohort with 74% reduction in risk of disease progression or death.
Graph showing PFS in gBRCAm cohort with 74% reduction in risk of disease progression or death.

*Censored subjects are indicated by open circles.

In the  non-gBRCAm Cohort, Median PFS With ZEJULA Was More Than 2x Longer Than With Placebo1,4,7

PFS in the non-gBRCAm cohort1,4,7*

Graph showing PFS in non-gBRCAm cohort with 55% reduction in risk o disease progression or death.
Graph showing PFS in non-gBRCAm cohort with 55% reduction in risk o disease progression or death.

*Includes 13% sBRCA patients.
Censored subjects are indicated by closed circles.

  • BRCAwt tumors are historically difficult to treat and are associated with poorer outcomes8,9
  • In the non-gBRCAm cohort, approximately 13.4% of women were known to be sBRCAm1,5

exploratory efficacy

An exploratory analysis of NOVA suggested that ZEJULA provided more time without disease progression compared with placebo, independent of baseline patient characteristics1,4,10

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.1,4,10

Similar magnitude of benefit seen within
key demographic and prognostic subgroups1,4,10

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

A reduction in the risk of disease progression or death was observed with ZEJULA1,4,10

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.1,4,10

Similar magnitude of benefit within
key demographic and prognostic subgroups1

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

In an exploratory analysis, improved median PFS was observed in patients with BRCAwt tumors who received ZEJULA compared to placebo1,5

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.7,10

PFS in the BRCAwt, HRDpos subpopulation10

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 open circles.

In an exploratory analysis, improved median PFS was observed in patients with non-gBRCAm tumors who received ZEJULA compared to placebo1,5

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.7,10

PFS in the non-gBRCAm, HRDneg subpopulation10

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 open circles.


quality of life

ZEJULA showed long-term tolerability after dose modification, including patients receiving treatment for >2 years1,5,11,12

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.

An exploratory analysis of NOVA suggested that ZEJULA did not adversely affect quality of life1,5

Based on the FOSI test, patients who received ZEJULA as maintenance treatment reported quality-of-life scores comparable to placebo during their treatment1,5

  • Values displayed in the chart below are adjusted means; a higher score suggests fewer symptoms5
  • 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 life10
  • 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 factors10

FOSI outcomes in the gBRCAm cohort5,10

Graph showing FOSI outcomes in the non-gBRCAm cohort.
Graph showing FOSI outcomes in the non-gBRCAm 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 discontinuation
  • Expand FOSI Scale

    FOSI: a validated, 8-item measure of patient-reported symptom response to treatment5,10,13

    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.

    Image showing 8-item measurement of FOSI: patient-reported response to treatment.
    Image showing 8-item measurement of FOSI: patient-reported response to treatment.

    FOSI, Functional Assessment of Cancer Therapy-Ovarian Symptoms Index
    Patients respond to their symptom experience over the past 7 days using a 5-point Likert scale scored from "not at all" (0) to "very much" (4).

FOSI outcomes in the non-gBRCAm cohort5,10

Graph showing FOSI outcomes in the gBRCAm cohort.
Graph showing FOSI outcomes in the gBRCAm 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 discontinuation
  • Expand FOSI Scale

    FOSI: a validated, 8-item measure of patient-reported symptom response to treatment5,10

    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.

    Image showing 8-item measurement of FOSI: patient-reported response to treatment.
    Image showing 8-item measurement of FOSI: patient-reported response to treatment.

    FOSI, Functional Assessment of Cancer Therapy-Ovarian Symptoms Index
    Patients respond to their symptom experience over the past 7 days using a 5-point Likert scale scored from "not at all" (0) to "very much" (4).