Safety

Safety Profile

PRIMA Clinical Study: An established safety and tolerability profile, in 1LM therapy of advanced ovarian cancer1,2

ARs reported in ≥10% of all patients receiving ZEJULA in PRIMA1*

Adverse reactions reported in ≥10% of patients in select grades 1-4 and 3-4 receiving ZEJULA (niraparib)

12% of patients discontinued treatment with ZEJULA due to ARs1,2

ARs resulting in discontinuation of ZEJULA in >1% of patients included thrombocytopenia (3.7%), anemia (1.9%), and nausea and neutropenia (1.2% each)1

ARs were managed with dose interruptions and modifications.

*All ARs consist of grouped preferred terms except for nausea, vomiting, decreased appetite, headache, and insomnia, which are single preferred terms.

CTCAE = Common Terminology Criteria for Adverse Events version 4.02.

Includes neutropenia, neutropenic infection, neutropenic sepsis, febrile neutropenia.

§Includes leukopenia, lymphocyte count decreased, lymphopenia, white blood cell count decreased.

Includes blood creatinine increased, blood urea increased, acute kidney injury, renal failure, and blood creatine increased.

Monitoring

Side effects of ZEJULA may be managed with dose interruption and modification1,2

  • In PRIMA, adverse events led to dose reduction or interruption in 80% of patients, most frequently from thrombocytopenia (56%), anemia (33%), and neutropenia (20%)1

Monitoring complete blood counts, blood pressure, and heart rate helps identify the need to dose modify1

Blood counts

Monitoring complete blood count infographic
Monitoring complete blood count infographic

Blood pressure and heart rate

Monitoring blood pressure and heart rate infographic
Monitoring blood pressure and heart rate infographic

#Monitor periodically. Per physician discretion.

Individualized Starting Dose

An individualized starting dose in 1LM, giving your patients a tailored dose from the start1,2

If baseline weight <170 lb OR platelets <150,000/μl

If baseline weight <170 lb OR platelets <150,000/μl

200

mg/day

mg/day

If baseline weight ≥170 lb AND platelets ≥150,000/μl

If baseline weight ≥170 lb AND platelets ≥150,000/μl

300

mg/day

mg/day

For patients with moderate hepatic impairment, reduce the starting dose of ZEJULA to 200 mg once daily. Monitor patients for hematologic toxicity and reduce the dose further, if needed.1

Safety icon

An individualized starting dose was observed to lower rates of select ARs while maintaining efficacy in an exploratory analysis1,3-5||

PRIMA prospectively evaluated the safety and efficacy of an individualized starting dose of either 200 mg or 300 mg, selected based on baseline weight and platelet count, as well as a fixed starting dose of 300 mg1,2

Rates of select grade 3-4 hematologic ARs1,3,4

Bar graph showing grades 3-4 hematologic adverse reactions in PRIMA
image

In PRIMA, patients in the overall and individualized populations experienced the same rates of grades 3-4 leukopenia.1

Rates of select grades 1-4 symptomatic gastrointestinal ARs4

Gastrointestinal adverse reactions bar graph

The efficacy of ZEJULA was maintained in the overall population, HRd, and BRCAm patients taking an individualized starting dose1,3,5||

Overall population

Overall population

31%

reduction in risk of progression or death observed with ZEJULA in patients in the overall population taking an individualized starting dose based on weight and platelet count vs placebo.1,3

HR, 0.69 (95% CI, 0.48-0.98)

HRd patients

HRd patients

61%

reduction in risk of progression or death observed with ZEJULA in HRd patients taking an individualized starting dose based on weight and platelet count vs placebo.1,3

HR, 0.39 (95% CI, 0.22-0.72)

BRCAm patients

BRCAm patients

71%

reduction in risk of progression or death observed with ZEJULA in BRCAm patients taking an individualized starting dose based on weight and platelet count vs placebo.5

HR, 0.29 (95% CI, 0.13-0.67)

||Exploratory subgroup analysis, not powered to detect a statistically significant treatment effect. Interpret results with caution.

Long-term Safety Data

In PRIMA, no new safety signals were reported in the 3.5-year median follow-up6

TEAE overview from 3.5-year follow-up of the overall population6

TEAEs ZEJULA (n=484) Placebo (n=244)
Any TEAE 99% 94%
Grade ≥3 73% 23%
Led to treatment discontinuation 14% 3%
Led to dose reduction 72% 9%
Led to dose interruption 80% 21%
Led to death 1% 1%

With 3.5-year median follow-up, the most common ARs (grades 1-4) in ≥20% of all patients who received ZEJULA in PRIMA were thrombocytopenia (67%), anemia (65%), nausea (58%), neutropenia (43%), constipation (42%), fatigue (37%), headache (28%), insomnia (26%), abdominal pain (25%), vomiting (24%), arthralgia (21%), hypertension (21%), and diarrhea (20%).6

ARs were consistent with the primary analysis and the known safety profile of ZEJULA1,2,6

The TEAE-related discontinuation rate was sustained with 3.5-year follow-up1,2,6**

**At the time of the primary analysis of PRIMA, 12% of patients discontinued treatment with ZEJULA due to ARs.1,2

ARs resulting in discontinuation of ZEJULA in >1% of patients included thrombocytopenia (3.7%), anemia (1.9%), and nausea and neutropenia (1.2% each).1

References

  1. ZEJULA (niraparib) Tablets. Prescribing Information. GSK; 2023.

  2. González‑Martín A, Pothuri B, Vergote I, et al. N Engl J Med. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962

  3. Mirza MR, González-Martín A, Graybill WS, et al. Cancer. 2023;1-10. doi:10.1002/cncr.34706

  4. Mirza MR, González-Martín A, Graybill WS, et al. [supplementary appendix]. Cancer. 2023;1-13. doi:10.1002/cncr.34706

  5. Korach J, Graybill W, Redondo A, et al. Int J Gynecol Cancer. 2020;30(suppl 4):A125-A126. doi:10.1136/ijgc-2020-ESGO.220

  6. González-Martín A, Pothuri B, Vergote I, et al. N Engl J Med. 2023;5,112908. doi:10.1016/j.ejca.2023.04.024