Literature

Clinical Pearls & Morning Reports


Published December 18, 2019

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In the PRIMA trial, how did niraparib compare with placebo as maintenance therapy after a response to chemotherapy in patients with advanced ovarian cancer? 

Most patients with advanced ovarian cancer do not have an effective treatment option to substantially reduce the risk of death or progressive disease after first-line chemotherapy. González-Martín et al. conducted the PRIMA trial, a randomized, double-blind, placebo-controlled phase 3 trial to assess the efficacy and safety of niraparib maintenance therapy after a response to platinum-based chemotherapy in patients with newly diagnosed advanced ovarian cancer. Read the Original Article here.

Clinical Pearls

Q: What is the standard treatment for newly diagnosed advanced epithelial ovarian cancer?

A: The standard treatment for newly diagnosed advanced epithelial ovarian cancer is surgical cytoreduction and systemic platinum–taxane combination chemotherapy. Unfortunately, up to 85% of the patients with advanced ovarian cancer have a disease recurrence after completing chemotherapy.

Q: How was “homologous-recombination deficiency” defined in the PRIMA trial?

A: Although a deleterious BRCA mutation indicates that a tumor has some form of homologous-recombination deficiency, patterns of genomic instability in the tumor can confer such a phenotype in the absence of a BRCA mutation. In the PRIMA trial, homologous-recombination deficiency was defined as the presence of a BRCA deleterious mutation, a score of at least 42 on the my-Choice test, or both. Test scores (which range from 1 to 100, with higher scores indicating a greater number of genomic abnormalities) represent a continuum on the basis of loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions.

 Morning Report Questions

Q: In the PRIMA trial, how did niraparib compare with placebo as maintenance therapy after a response to chemotherapy in patients with advanced ovarian cancer?

A: The authors found that patients with newly diagnosed advanced ovarian cancer who received niraparib after having a response to first-line platinum-based chemotherapy had significantly longer progression-free survival than those who received placebo in the overall population. Within the population with homologous-recombination deficiency, the median duration of progression-free survival was 22.1 months in the niraparib group and 10.9 months in the placebo group (hazard ratio, 0.40; 95% CI, 0.27 to 0.62) in the subgroup with BRCA mutations and 19.6 months and 8.2 months, respectively (hazard ratio, 0.50; 95% CI, 0.31 to 0.83), in the subgroup without BRCA mutations. The sensitivity to niraparib is lower in patients who have tumors with homologous-recombination proficiency than in those who have tumors with homologous-recombination deficiency. In the PRIMA trial, in the subgroup of patients with homologous-recombination proficiency, the median duration of progression-free survival was 8.1 months in the niraparib group and 5.4 months in the placebo group (hazard ratio, 0.68; 95% CI, 0.49 to 0.94).

Q: What were some of the most common adverse events of grade 3 or higher in the niraparib group in the PRIMA trial?

A: Among the most common grade 3 or higher adverse events in the niraparib group were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). Myelosuppressive adverse events were the main reason for discontinuation but were infrequent (4.3% for thrombocytopenia in the niraparib group).

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