Clinical Pearls & Morning Reports
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.
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.
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).
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).