Niraparib in the PRIMA Trial
Shannon Westin, MD, discusses niraparib and its relation to the design, efficacy, and practical implications of the PRIMA trial.
Shannon Westin, MD: The choice to utilize niraparib as a maintenance strategy both in patients that have either a BRCA1 or a BRCA2 mutation, patients that have homologous or combination-deficient disease, or even an all-inclusive population after response to therapy, is based on the PRIMA trial. This was a large, randomized, controlled trial that took patients who were from a bit more of a high-risk patient population. The researchers selected patients who had either a stage IV disease, like our patient, or stage III disease but residual tumors at the end of their surgery.
They randomized those patients after the completion of chemotherapy, with them taking either niraparib or a placebo. It was a 2:1 randomization, and they got the niraparib once a day. They were followed very closely with imaging every 12 weeks to look at the primary end point, which was progression-free survival. What is important about this trial is that there were 2 primary end points. The 2 primary end points included progression-free survival for patients who had a tumor that was homologous or combination deficient, as well as progression-free survival in the overall patient population.
Those were the 2 primary end points that the study was powered for; the researchers assessed this by blinded independent central review. They defined progression-free survival as beginning at the time of randomization until the earliest date of objective disease progression on imaging. The secondary end points of importance were overall survival, or time to subsequent therapy, and progression-free survival. The researchers also looked at pharmacokinetics and, importantly, patient-reported outcomes. These are obviously very important when we are looking at maintenance strategies, because we want to make sure we help people live longer without disease, but also that we are not harming them with other additional adverse effects and adverse events. That was the basic design of the PRIMA trial, and it did meet both of its primary end points.
As I mentioned before in our discussion, we did see a reduction in the risk of progression in both the group that had homologous or combination deficiency; there was reduction in the risk of progression of about 60%. In the group of all comers, we still saw a reduction in the risk of progression, but that reduction was not quite as profound. We saw about a 40% reduction in the risk of progression in the group that was treated with niraparib, so that was obviously very exciting. The actual median difference for the group that had HRD [homologous recombination deficiency] was about an 11-month difference. In the group that had all comers, there was about a 5-month difference.
The study definitely met both its primary end points and had a significant benefit in improving progression-free survival for the entire population. The reason you heard me chat about using that homologous or combination deficiency testing is that, in some subset analyses, study is not built for it, but this testing can still be informative. In subset analyses, there was not as profound a difference between patients who had truly homologous or combination proficient disease. There was a reduction in the risk of progression, but it was on average after a few months.
There is some trouble with this. First, this study is not powered to show difference, but you do not know where your patient would be on these lines. A portion of patients with testing said their tumor was homologous or combination proficient, yet they do get benefits from the PARP inhibitor. Why is that? It could be that the test is not as good as we want it to be. It is still a work in progress. It could be that there is something else in the patient’s tumor that is yielding benefits from the PARP inhibitor. We do not know that. For me, if I have a patient who has had testing that reveals a homologous or combination proficient disease, and I haven’t given her another maintenance treatment like bevacizumab, and she wants to do something, then we will have an honest conversation about what her potential benefit is from the niraparib. Does the patient want to pursue that? Some patients just want to do everything they can. Certainly, you’ve got an FDA approval here. You have data to show that there was an improvement. It is up to you to interpret how clinically meaningful that is, and it is up to you to help the patient decide what she wants to go ahead with.
Transcript edited for clarity.
Case: A 68-Year-Old Woman With Recurrent Ovarian Cancer
Initial Presentation
- A 68-year-old female presented with abdominal bloating, discomfort and decreased appetite
- PMH: unremarkable, postmenopausal; no known family history of cancer
- PE: abdominal distention, right lower quadrant tenderness on palpation
Clinical work-up
- Pelvic exam with transvaginal ultrasound showed a right ovarian mass
- Chest/abdomen/pelvis CT with contrast revealed a right adnexal 4-cm mass, inguinal lymph node involvement and ascites, no pleural effusion
- Lymph node, adnexal mass biopsy, and paracentesis (1500 cc) cytology confirmed high-grade epithelial ovarian cancer
- Germline molecular testing: HRD+, BRCA1/2-
- CA-125, 385 U/mL
- Diagnosis: Stage 4, high-grade epithelial ovarian cancer
- ECOG PS 0
Treatment
- Patient underwent TAH/BSO, lymph node dissection, with optimal debulking; R0
- IP/IV paclitaxel/carboplatin; PR
- Followed by niraparib maintenance
