Maintenance Treatment of Recurrent Ovarian Cancer

NOVA

Study Design

NOVA Is 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
 

Infographic depicting the study design of the phase 3 trial for ZEJULA
Infographic depicting the study design of the phase 3 trial for ZEJULA

 

  • 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) comprised the majority of patients. Approximately 13% of women in the non-gBRCAmut cohort had tumors that were known to be sBRCAmut.1

The non-gBRCAmut 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.1,5

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.1,5

§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-125.1,5

||Additional diagnostic tests included histology/cytology, ultrasound, endoscopy, and PET.1,5, 6
 

ZEJULA Was Evaluated With the Clinical Rigor of a Phase 3 Trial (NOVA) That Independently Tested Treatment Benefit in gBRCAmut and Non-gBRCAmut Cohorts1,4

In the non-gBRCAmut cohort, additional exploratory analyses were conducted in HRDpos and HRDneg subpopulations1

Chart representing the various patient cohorts studied in the NOVA trial
Chart representing the various patient cohorts studied in the NOVA trial


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.1

In the NOVA trial, patient demographics were well-balanced across treatment arms and representative of women seen in clinical practice1,4,5

Knowledge card with demographic information of patients involved in the clinical trial
Knowledge card with demographic information of patients involved in the clinical trial

 

  • 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 maintenance1,5,6

More NOVA data: NOVA: Baseline Patient Characteristics


BRCA, breast cancer susceptibility gene; BRCAwt, BRCA wild type; CA-125, cancer antigen 125; CR, complete response; CT, computed tomography; gBRCAmut, germline BRCA mutated; 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.

Efficacy gBRCAmut

NOVA: In the gBRCAmut Cohort, the Median PFS Was Nearly 4x Longer Than Placebo (n=203)1,5,7

PFS in the gBRCAmut cohort5
Chart indicating that estimated long term PFS of 24 months was 42% with ZEJULA and 16% with placebo in gBRCAmut cohort of patients

aCensored subjects are indicated by closed circles.

In an Exploratory Analysis of the NOVA trial, ZEJULA Demonstrated More Time Without Disease Progression Compared to Placebo, Independent of Baseline Patient Characteristics1,5,6

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.1,5,6

Similar magnitude of benefit within key demographic and prognostic subgroups1
Table depicting that ZEJULA® provided similar benefits within key demographic and prognostic subgroups

CI, confidence interval; CR, complete response; gBRCAmut, germline BRCA mutated; HR, hazard ratio; HRD, homologous recombination deficiency; non-gBRCAmut, not germline BRCA mutated; PFS, progression-free survival; PR, partial response.

Efficacy non-gBRCAmut

NOVA: ZEJULA May Give You More Options When Treating Patients by Sustaining Platinum Eligibility6

In the non-gBRCAmut cohort, the median PFS with ZEJULA was more than 2x longer than placebo1,5

PFS in the non-gBRCAmut cohort1,5,7
Chart indicating that estimated long term PFS of 24 months was 27% with ZEJULA® and 12% with placebo in non-gBRCAmut cohort of patients

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

  • BRCA wild type tumors are historically difficult to treat and are associated with poorer outcomes8,9
  • In the non-gBRCAmut cohort, approximately 13.4% of women were known to be sBRCAmut1

Continued platinum eligibility was achieved in 73% of non-gBRCAmut patients receiving ZEJULA and 47% of patients receiving placebo, as demonstrated in an exploratory analysis6

Platinum eligibility was defined by a platinum-free interval of ≥6 months.10

This analysis is exploratory in nature; it does not control for type 1 error and is not powered to determine treatment effect.6

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In an exploratory analysis, ZEJULA demonstrated improved median PFS for patients with BRCAwt tumors1,6,7

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.6

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PFS in the BRCA wild-type, HRDpos subpopulation6

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a Censored subjects are indicated by closed circles.

Continued platinum eligibility was achieved in 70% of BRCAwt patients receiving ZEJULA and 45% of patients receiving placebo as demonstrated in an exploratory analysis6

Platinum eligibility was defined by a platinum-free interval of ≥6 months.10

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

Chart 2.png

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In an Exploratory Analysis of NOVA, ZEJULA Demonstrated More Time Without Disease Progression, Independent of Baseline Patient Characteristics1,5,6

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.1,5,6
 

NOVA: Similar magnitude of benefit within key demographic and prognostic subgroups1
Table depicting that ZEJULA® provided similar benefits within key demographic and prognostic subgroups

BRCA, breast cancer susceptibility gene; 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; sBRCAmut, somatic BRCA mutated.

Tolerability and Quality-of-Life

ZEJULA Showed Long-term Tolerability in the NOVA Trial After Dose Modification, Including Patients Receiving Treatment for >2 Years1

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.

In an Exploratory Analysis of NOVA, quality of life was similar between patients receiving placebo and those receiving active treatment1

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

  • Values displayed in the chart below are adjusted means; a higher score suggests fewer symptoms
  • 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 non-drug factors6

More data: See FOSI Scale

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FOSI outcomes in the gBRCAmut cohort1

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FOSI outcomes in the non-gBRCAmut cohort1

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BRCA, breast cancer susceptibility gene; C, cycle; FOSI, Functional Assessment of Cancer Therapy—Ovarian Symptom Index; gBRCAmut, germline breast cancer susceptibility gene mutated; non-gBRCAmut, not germline BRCA mutated; SE, standard error.

  • 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 group6
  • Patients were assessed at baseline, every 8 weeks for the first year, every 12 weeks thereafter during treatment, and then 6-10 weeks after treatment discontinuation6

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

Dosing information

DOSE MODIFICATIONS

See recommendations for dose adjustments

Review Dosing
Safety data

SAFETY DATA

Learn about the safety and tolerability of ZEJULA

See Safety

References: 1. Mirza MR, Monk BJ, Herrstedt J, et al; ENGOT-OV16/NOVA Investigators. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375(22):2154-2164, and Supplementary Appendix. 2. Coleman RL, Oza AM, Lorusso D, et al; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10106):1949-1961. doi: 10.1016/S0140-6736(17)32440-6. 3. Pujade-Lauraine E, Ledermann JA, Selle E, et al; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(9):1274-1284. doi: 10.1016/S1470-2045(17)30469-2. 4. Mahner S, Mirza MR, Moore K, et al. ENGOT-OV16/NOVA: results for secondary efficacy endpoints of niraparib treatment in ovarian cancer. Slide deck presented at: Annual Meeting on Women’s Cancer; March 12-15, 2017; National Harbor, MD. 5. ZEJULA (niraparib) [package insert]. Waltham, MA: GSK, Inc; October 2019. 6. Data on file. TESARO, Inc. 7. Matulonis UA, Herrstedt J, Tinker AV, et al. Long-term benefit of niraparib treatment of recurrent ovarian cancer (OC). Poster presented at: American Society of Clinical Oncology Annual Meeting; June 2-6, 2017; Chicago, IL. Poster 5534. 8. Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434(7035):913-917. 9. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917-921. 10. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian Cancer including Fallopian Tube Cancer and Primary Peritoneal Cancer V.4.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed January 16, 2018. To view the most recent and complete version of the guidelines, go online to NCCN.org.