Clinical trialPhase 3Ovarian cancer

Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial

Annals of Oncology · 2024733 patients in the overall population (487 niraparib and 246 placebo)

Monk B, Barretina-Ginesta M, Pothuri B, Vergote I, Graybill W, Mirza M, et al. Annals of Oncology. 2024. 35:981-992

Study type: Clinical trial
Study name: PRIMA/ENGOT-OV26/GOG-3012
Phase: Phase 3
Design: Randomised 2:1 placebo-controlled trial
Sample size: 733 patients in the overall population (487 niraparib and 246 placebo)
Source: Annals of Oncology · 2024

In plain words

This study looked at patients with advanced ovarian cancer who had responded to first-line chemotherapy and then took niraparib or a placebo to help keep the benefit of treatment. After about 74 months of follow-up, overall survival was no different between the two groups. However, at five years, a higher percentage of patients in the niraparib group were living without the disease getting worse, and this difference was greater in patients with homologous recombination deficiency (a DNA repair defect in the tumour). No new or unexpected side effects were seen.

Key results

1.01 (95% CI 0.84–1.23)

Overall survival hazard ratio, overall population

P=0.8834; niraparib (n=487) vs placebo (n=246)

0.95 (95% CI 0.70–1.29)

Overall survival hazard ratio, HRd population

n=373

0.93 (95% CI 0.69–1.26)

Overall survival hazard ratio, HRp population

n=249

11.7% vs 37.8%

Subsequent PARP inhibitor therapy, overall population

Niraparib vs placebo

15.8% vs 48.4%

Subsequent PARP inhibitor therapy, HRd population

Niraparib vs placebo

22% vs 12%

Five-year PFS rate, overall population

Numerically favouring niraparib

35% vs 16%

Five-year PFS rate, HRd population

Numerically favouring niraparib

2.3% vs 1.6%

Incidence of myelodysplastic syndromes/acute myeloid leukaemia (MDS/AML)

Below 2.5%; niraparib vs placebo

73.9 months

Median follow-up

Dose and schedule cards

Niraparib maintenance (PRIMA)

Advanced disease with complete or partial response to first-line platinum; current FDA label: HRD-positive only; ESMO: can also be considered in HRD-negative disease [I, B]Cycle length: ContinuousOn the page “Ovarian cancer” · First line: maintenance therapy (based on BRCA and HRD)

Advanced disease with complete or partial response to first-line platinum; current FDA label: HRD-positive only; ESMO: can also be considered in HRD-negative disease [I, B]

Drug	Dose	Route	Schedule
Niraparib	Weight less than 77 kg or platelets less than 150,000: 200 mg; weight 77 kg or more and platelets 150,000 or more: 300 mg	Oral, once daily (taking it at bedtime helps reduce nausea)	Continuously

Cycle length: Continuous
Duration: Start no later than 12 weeks after the last platinum dose; label: until progression or toxicity; ESMO: 3 years

Monitoring: complete blood count weekly for the first month, monthly for the next 11 months and periodically thereafter; blood pressure and heart rate at least weekly for the first 2 months, then monthly for the first year. Platelets below 100,000: withhold for up to 28 days with weekly blood counts. Dose reduction: 200 → 100 mg; 300 → 200 → 100 mg; moderate hepatic impairment: 200 mg. In PRIMA, overall survival did not differ (HR 1.01).

On the page “Ovarian cancer” · First line: maintenance therapy (based on BRCA and HRD)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Niraparib (487 patients)

Niraparib orally once daily. At the start of the study, a fixed dose of 300 mg (475 patients); from November 2017, an individualised starting dose: 200 mg for baseline weight below 77 kg or platelets below 150,000 per microlitre, and 300 mg for weight 77 kg or more and platelets 150,000 or more (258 patients). Treatment until progression or unacceptable toxicity, with a planned duration of 3 years (continuation beyond 3 years was allowed if the investigator judged it beneficial). Crossover between arms was not allowed.

2Placebo (246 patients)

Placebo orally once daily on the same schedule.

Source of the regimen details: Full text of the paper (Ann Oncol 2024; PMC11934258, Methods section and Table 3)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients aged 18 and older with newly diagnosed advanced ovarian, fallopian tube or primary peritoneal cancer (high-grade serous or endometrioid, FIGO stage III–IV) who had a complete or partial response to first-line platinum chemotherapy, regardless of HRD test result (MyChoice CDx). Randomised 2:1 within 12 weeks of the last dose of first-line chemotherapy, stratified by response to first-line treatment, receipt of neoadjuvant chemotherapy and HRD status. HRd population: 373 patients; HRp: 249 patients.

Endpoints

In this final report, overall survival (OS) was tested hierarchically (first the overall population, then the HRd population). Other secondary endpoints and long-term safety were also assessed. The trial's primary endpoint, progression-free survival (PFS), had already been met. An updated ad hoc analysis of investigator-assessed PFS was also performed (data cutoff: 8 April 2024).

Safety and side effects

In the final analysis (patients who received at least one dose; 484 versus 244): treatment-emergent grade 3 or higher adverse events 73.8% versus 23.8% and treatment-related 66.9% versus 8.6%; serious adverse events 40.9% versus 17.6%; dose interruption 80.8% versus 23.0%, dose reduction 71.7% versus 10.2% and discontinuation due to adverse events 16.3% versus 3.7%. The most common grade 3 or higher events were haematological. The incidence of MDS/AML was below 2.5% (2.3% versus 1.6%), and no new safety signal was seen.

Clinical significance and place in guidelines

This final analysis shows that the progression-free survival benefit of niraparib did not translate into improved overall survival. Some patients in the placebo group later received a PARP inhibitor, which must be considered when interpreting OS. These findings should be weighed together with the PFS and long-term safety data when deciding on maintenance therapy, especially in HRd patients. The status of approvals and current guideline recommendations should be checked separately, as the abstract does not address them.

Limitations

OS showed no difference. Some patients in the placebo group received subsequent PARP inhibitor therapy (37.8% in the overall population and 48.4% in the HRd population, versus 11.7% and 15.8% in the niraparib group). The updated PFS analysis was ad hoc. Five-year PFS rates are reported numerically only.

Original article (DOI)PubMed

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.