ZEJULA Was Evaluated With the Clinical Rigor of a Phase 3 Trial That Independently Tested Treatment Benefit in gBRCAmut and Non-gBRCAmut Populations1,2

The NOVA trial included 553 women with recurrent ovarian, fallopian tube, or primary peritoneal cancer following complete or partial response (CR or PR) to second-line or later platinum-based chemotherapy1

  • The prospectively defined primary end point was PFS as assessed by blinded, independent, central review of both clinical AND radiologic progression, with a frequent scan interval2,3

Phase 3 trial design1

Chart showing recurrent epithelial, fallopian tube, or primary peritoneal cancer following complete or partial response to platinum-based therapy

a The non-gBRCAmut cohort included patients whose tumors were somatic BRCA mutated or BRCA wild type. Approximately 13% of women in the non-gBRCAmut cohort had tumors that were known to be sBRCAmut.2

b 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).1 Patients continued to receive ZEJULA or placebo until disease progression, unacceptable toxicity, death, withdrawal of consent, or loss to follow-up, whichever came first.2

c CT or MRI was performed at baseline and every 8 weeks through cycle 14, then every 12 weeks until treatment discontinuation.2 PFS was determined by central independent assessment per RECIST v1.1, along with more conservative measures of clinical signs and symptoms and increasing CA-125.1

BRCA breast cancer susceptibility gene; CA-125, cancer antigen 125; CR, complete response; CT, computed tomography; gBRCAmut, germline BRCA mutated; MRI, magnetic resonance imaging; non-gBRCAmut, not germline BRCA mutated; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria In Solid Tumors; sBRCAmut, somatic BRCA mutated.

 

PFS was measured from time of randomization to time of disease progression or death1,2

  • PFS was determined to occur at the earlier of either radiographic progression or clinical signs and symptoms and increasing CA-1253
CA-125, cancer antigen 125; PFS, progression-free survival
 

 

The NOVA Patient Population Included Women With or Without BRCAmut Tumors1

In the non-gBRCAmut cohort, women whose tumors had no BRCA mutation and women whose tumors were HRDneg comprised the majority of patients2

Chart showing the non-gBRCAmut cohort, women whose tumors had no BRCA mutation and women whose tumors were HRDneg comprised the majority of patients
BRCA, breast cancer susceptibility gene; BRCAmut, BRCA mutated; CR, complete response; gBRCAmut, germline BRCA mutated; HRD, homologous recombination deficiency; HRDneg, HRD negative; HRDpos, HRD positive; non-gBRCAmut, not germline BRCA mutated; PR, partial response; sBRCAmut, somatic BRCA mutated.

Patient population encompassed women who achieved CR or PR, as well as those who received prior bevacizumab1

  • The median age ranged from 57 to 63 years2
  • Approximately 50% of all patients were in PR to their most recent platinum-based regimen1
  • Approximately 40% of all patients had 3 or more lines of treatment1
  • 26% of those treated with ZEJULA had received prior bevacizumab in conjunction with the penultimate or last platinum regimen1
  • Of those, 16% received ZEJULA as switch maintenance after receiving bevacizumab with their last platinum therapy2,3
  • 7.6% of all patients had a measurable tumor >2 cm4

CR, complete response; PR, partial response.

For women whose recurrent epithelial ovarian, fallopian tube, or primary peritoneal ovarian cancer responded with a CR or PR to platinum-based chemotherapy1

Median PFS With ZEJULA Was Nearly 4× Higher Than Placebo in the gBRCAmut Cohort1

PFS in the gBRCAmut cohort1

Graph showing PFS in the gBRCAmut cohort
aCensored subjects are indicated by open circles.
BRCA, breast cancer susceptibility gene; CI, confidence interval; HR, hazard ratio; non-gBRCAmut, not germlineBRCAmutated; PFS, progression-free survival.
  • In the gBRCAmut cohort, it is estimated that long-term PFS of 24 months was achieved in 42% of women receiving ZEJULA compared with 16% receiving placebo3,5

 

Median PFS With ZEJULA Was More Than 2× Higher Than Placebo in the Non-gBRCAmut Cohort1

  • BRCA wild-type tumors are historically difficult to treat and are associated with poorer outcomes6
  • In the non-gBRCAmut cohort, approximately 71% of women had tumors that were known to be BRCA wild type2

PFS in the non-gBRCAmut cohort1

Graph showing PFS in the non-gBRCAmut cohort
aCensored subjects are indicated by open circles.
BRCA, breast cancer susceptibility gene; CI, confidence interval; HR, hazard ratio; non-gBRCAmut, not germlineBRCAmutated; PFS, progression-free survival.
  • In the non-gBRCAmut cohort, it is estimated that long-term PFS of 24 months was achieved in 27% of women receiving ZEJULA compared with 12% receiving placebo3,5

 

ZEJULA Showed Meaningful Clinical Benefit in a Phase 3 Study in the BRCA Wild-Type Population2

A subgroup analysis showed PFS improvement across subpopulations evaluated2

  • 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 subgroup3
  • BRCA wild-type tumors are historically difficult to treat and are associated with poorer outcomes

PFS in the BRCA wild-type, HRDpos subpopulation2,7

Graph showing PFS in the BRCA wild-type, HRDpos subpopulation
a Censored subjects are indicated by open circles.
BRCA, breast cancer susceptibility gene; CI, confidence interval; HR, hazard ratio; non-gBRCAmut, not germline BRCA mutated; PFS, progression-free survival.
  • In the BRCA wild-type, HRDpos subpopulation, it is estimated that long-term PFS of 24 months would be achieved in 22% of women receiving ZEJULA compared with 6% receiving placebo3

PFS in the BRCA wild-type, HRDneg subpopulation2,7

Graph showing PFS in the BRCA wild-type, HRDneg subpopulation
  • In the BRCA wild-type, HRDneg subpopulation, it is estimated that long-term PFS of 24 months would be achieved in 19% of women receiving ZEJULA compared with 7% receiving placebo3,5
a Censored subjects are indicated by open circles. BRCA, breast cancer susceptibility gene; CI, confidence interval; gBRCAmut, germline BRCA mutated; HR, hazard ratio; HRD, homologous recombination deficiency; HRDneg, HRD negative; HRDpos, HRD positive; PFS, progression-free survival; sBRCAmut, somatic BRCA mutated.

 

ZEJULA Provided More Time Without Disease Progression, Independent of Baseline Patient Characteristics1,2

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.3

Similar magnitude of benefit within key demographic and prognostic subgroups2

Chart showing an explatory analysis how ZEJULA provided more time without disease progression
BRCA, breast cancer susceptibility gene; CI, confidence interval; CR, complete response; gBRCAmut, germline BRCA mutated; HR, hazard ratio; non-gBRCAmut, not germline BRCA mutated; PR, partial response.

In an exploratory analysis

ZEJULA Was Not Shown to Adversely Affect Quality of Life2

Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI): A validated, 8-item measure of symptom response to treatment for ovarian cancer. 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).

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 factors.

  • 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 group2
  • 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 discontinuation3
Chart showing adverse affect quality of life

 

Based on the FOSI test, patients who received ZEJULA as maintenance treatment retained a quality of life comparable to placebo during their treatment2

  • Values displayed in the charts below are adjusted means; a higher score indicates fewer symptoms

FOSI in the gBRCAmut cohorta

Graph showing FOSI in the gBRCAmut cohort

 

FOSI in the non- gBRCAmut cohorta

Graph showing FOSI in the non- gBRCAmut cohort
a Adapted from Mirza MR et al, 2016.
BRCA, breast cancer susceptibility gene; C, cycle; FOSI, Functional Assessment of Cancer Therapy–Ovarian Symptom Index; gBRCAmut, germline BRCA mutated; non-gBRCAmut, not germline BRCA mutated; SE, standard error.
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 factors.

 

Please see Important Safety Information below and full Prescribing Information.

See safety and tolerability data

References1. ZEJULA [package insert]. Waltham, MA: TESARO, Inc; 2017. 2. Mirza MR et al; ENGOT-OV16/NOVA Investigators. N Engl J Med. 2016;375(22):2154-2164. 3. Data on file. TESARO, Inc. 4. Mahner S et al. Presented at: 2017 Annual Meeting on Women’s Cancer 2017; March 12-15, 2017; National Harbor, MD. 5. Matulonis UA et al. Poster presented at: American Society of Clinical Oncology Annual Meeting; June 2-6, 2017; Chicago, IL. Poster 5534. 6. Hollis RL et al. Onco Targets Ther. 2017(10):2539-2551. 7. Mirza M et al. Presented at: 41st European Society for Medical Oncology Congress; October 7-11, 2016; Copenhagen, Denmark. Abstract LBA3_PR. 8. FOSI: for patients with ovarian cancer; A FACT-Ovarian Symptom Index (a subset of FACT-O containing 8 items). FACIT.org. http://www.facit.orgffacitorg/questionaires. Published November 16, 2007. Accessed October 6, 2017.