ZEJULA Improved PFS in Both gBRCAmut and non-gBRCAmut Cohorts1

ZEJULA was evaluated in a double-blind, placebo-controlled phase 3 trial1

Double-blind, placebo-controlled phase 3 trial schema Double-blind, placebo-controlled phase 3 trial schema

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

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 (complete response and partial response).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 primarily by central independent assessment per RECIST v1.1. In some cases, clinical signs and symptoms and increasing CA-125 were also applied.1

  • Trial included women with and without a germline BRCA mutation (gBRCAmut and non-gBRCAmut)1
  • 51% of all patients were in complete response to most recent platinum-based regimen1
  • 26% of patients treated with ZEJULA had received prior bevacizumab therapy1
Please see Important Safety Information below and full Prescribing Information.

Results for Progression-Free Survival (PFS), the Primary End Point1

The NOVA trial demonstrated a statistically significant improvement in PFS for patients receiving ZEJULA compared with patients receiving placebo in both the gBRCAmut and the non-gBRCAmut cohorts.

In the gBRCAmut cohort, ZEJULA reduced the risk of disease progression or death by 74% (HR = 0.26; 95% CI, 0.17-0.41), P < 0.00011

  • 21.0 months median PFS with ZEJULA in the gBRCAmut cohort vs 5.5 months with placebo

PFS in the gBRCAmut cohort

Increased PFS in the gBRCAmut cohort KM curve

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

In the non-gBRCAmut cohort, ZEJULA reduced the risk of disease progression or death by 55% (HR = 0.45; 95% CI, 0.34-0.61), P < 0.00011

Approximately 13% of women in the non-gBRCAmut cohort had tumors that were known to be sBRCAmut.2

  • 9.3 months median PFS with ZEJULA in the non-gBRCAmut cohort vs 3.9 months with placebo1

PFS in the non-gBRCAmut cohort1

Increased PFS in the non-gBRCAmut cohort KM curve

BRCA, breast cancer susceptibility gene; CI, confidence interval; HR, hazard ratio; non-gBRCAmut, not germline BRCA mutated; PFS, progression-free survival; sBRCAmut, somatic BRCA mutated.

See safety and tolerability data
Indication and Important Safety Information for ZEJULA

Indication

ZEJULA is indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Important Safety Information

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including some fatal cases, was reported in 1.4% of patients receiving ZEJULA vs 1.1% of patients receiving placebo in Trial 1 (NOVA), and 0.9% of patients treated with ZEJULA in all clinical studies. The duration of ZEJULA treatment in patients prior to developing MDS/AML varied from <1 month to 2 years. All patients had received prior chemotherapy with platinum and some had also received other DNA damaging agents and radiotherapy. Discontinue ZEJULA if MDS/AML is confirmed.

Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients receiving ZEJULA. Grade ≥3 thrombocytopenia, anemia and neutropenia were reported in 29%, 25%, and 20% of patients receiving ZEJULA, respectively. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, in 3%, 1%, and 2% of patients, respectively. 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 of treatment, 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 9% of patients receiving ZEJULA vs 2% of patients receiving placebo in Trial 1, with discontinuation occurring in <1% of patients. Monitor blood pressure and heart rate 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.

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. Because of the potential for serious adverse reactions from ZEJULA in breastfed infants, advise lactating women to not breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose.

In clinical studies, the most common adverse reactions (Grades 1-4) in ≥10% of patients included: thrombocytopenia (61%), anemia (50%), neutropenia (30%), leukopenia (17%), palpitations (10%), nausea (74%), constipation (40%), vomiting (34%), abdominal pain/distention (33%), mucositis/stomatitis (20%), diarrhea (20%), dyspepsia (18%), dry mouth (10%), fatigue/asthenia (57%), decreased appetite (25%), urinary tract infection (13%), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation (10%), myalgia (19%), back pain (18%), arthralgia (13%), headache (26%), dizziness (18%), dysgeusia (10%), insomnia (27%), anxiety (11%), nasopharyngitis (23%), dyspnea (20%), cough (16%), rash (21%) and hypertension (20%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients included: decrease in hemoglobin (85%), decrease in platelet count (72%), decrease in white blood cell count (66%), decrease in absolute neutrophil count (53%), increase in AST (36%) and increase in ALT (28%).

References: 1. ZEJULA [package insert]. Waltham, MA: TESARO, Inc; 2017. 2. 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.