Study: Niraparib increases progression-free survival in patients with newly diagnosed ovarian cancer

IN-DEPTH REVIEW OF RESEARCH

Study background:

Clinical benefit with PARP inhibitors has been observed for patients with BRCA mutations, in both the up-front setting and the recurrent setting.  Some recent trials have shown that niraparib is effective in some patients with normal BRCA genes in their tumors. These trials resulted in two FDA approvals:

• In 2017 niraparib was approved as a maintenance treatment for women with recurrent ovarian cancer who responded to platinum-based chemotherapy, even in the absence of a germline or somatic BRCA mutation.
• In 2019, niraparib was approved as fourth-line therapy for women with advanced ovarian cancer with a type of DNA repair deficiency called homologous recombination deficiency (HRD).

The researchers conducting the PRIMA trial wanted to know if the observed clinical benefit of niraparib could be extended to all patients with advanced ovarian cancer including those patients whose tumors had HRD (with or without a BRCA mutation) and those patients whose tumors did not have HRD.

Researchers of this study wanted to know:

How well niraparib works as a maintenance therapy following front-line platinum-based chemotherapy in patients with Stage III or IV ovarian cancer (including fallopian and peritoneal cancers).

• The primary end-point was progression-free survival in both patients whose tumors had HRD and in patients in the overall population.
• The secondary end-point was overall survival.

Populations looked at in this study:

This study randomized 733 newly diagnosed ovarian cancer patients to receive niraparib (487 patients) or a placebo or sugar pill (246 patients) once daily following chemotherapy.

Of the patients who were randomized and received either niraparib or a placebo:

• 373/733 (51%) had tumors with HRD with Myriad’s myChoice testing.
  • 223/373 (60%) had tumors with a BRCA mutation (either inherited or acquired).
  • 150/373 (40%) had tumors without a BRCA mutation.

Study design:

This phase III trial was conducted in 20 countries at 181 clinical sites from July 2016-June 2018. Within 12 weeks of completing the last dose of chemotherapy, patients were randomized in a 2:1 ratio to receive oral niraparib or a placebo once daily for 36 months or until their disease progressed. Computed tomography (a form of tomography in which a computer controls the X-ray source and detectors, processes the data and produces the image) or MRI was used to assess disease every 12 weeks until the treatment ended or was discontinued.

Study findings:

Among the 373 patients whose tumors had HRD:

• The median progression-free survival was longer in the niraparib group than in the placebo group (21.9 months v. 10.4 months).
• In the BRCA-mutated group (a subset of the HRD group), median progression-free survival was longer in the niraparib group than in the placebo group (19.6 months v 8.2 months).

In the overall population (all 733 patients):

• The median progression-free survival was longer in the niraparib group than in the placebo group (13.8 months vs. 8.2 months).
• At 24 months, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group.

The most common adverse events were anemia (decrease in red blood cells), thrombocytopenia (decrease in blood platelets which help healing), and neutropenia (decrease in neutrophils which help fight infection).

Limitations:

While not a limitation of this study, it is important to note that among the 484 patients randomized to receive niraparib, just over 18% discontinued niraparib due to adverse events (58) or for other reasons (31). Among the 244 patients randomized to receive a placebo, a little over 5% discontinued the trial due to adverse events (5) or for other reasons (8).  However, patient withdrawal from ovarian cancer trials is neither uncommon nor unique to this study. These patients all had advanced disease and had undergone multiple rounds of chemotherapy. Importantly, there were a total of 626 woman who remained on the trial for which there is data.

Conclusions:

The results of this trial showed that treatment with niraparib provides longer progression-free survival than placebo for the overall patient population.  Clinical benefit was not limited to the subset of patients whose tumors were HRD, however the largest benefit was seen in HRD cancers.

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Posted 11/5/19