Niraparib demonstrated clinically relevant activity among women with heavily pretreated ovarian cancer, particularly those with homologous recombination deficiency-positive, platinum-sensitive disease, according to findings from the phase 2 QUADRA study published in The Lancet Oncology.
The results, which also showed no new safety signals, support extending the use of poly(ADP-ribose) polymerase (PARP) inhibitors to a wider population of women with late-line ovarian cancer, including those without BRCAmutations, according to the researchers.
“This is another piece of the puzzle that helps our patients live longer,â€Â Kathleen Moore, MD, associate director of clinical research at Stephenson Cancer Center at University of Oklahoma College of Medicine, said in a press release. “There haven’t been a lot of studies done on patients without BRCA mutations who have received four, five, six or more lines of chemotherapy. That’s who this trial sought to study.â€
As many as 25% of women without a BRCA mutation can develop homologous recombination deficiency (HRD), which means they can derive benefits from PARP inhibitors such as niraparib (Zejula, Tesaro).
In the multicenter, open-label, single-arm, phase 2 study, Moore and colleagues enrolled 463 women aged 18 years and older (median age, 65 years; range, 29-91) with metastatic, relapsed, high-grade serous (grade 2 or 3) epithelial ovarian, fallopian tube or primary peritoneal cancer who had undergone at least three prior chemotherapy regimens. Patients had ECOG performance status of 0 or 1 and adequate organ function and had received a median four (interquartile range [IQR], 3-5) previous lines of treatment.
The study was conducted at 56 sites in the United States and Canada.
Women received 300 mg oral niraparib once daily starting on day 1 and continuously through each 28-day cycle until disease progression, unacceptable toxicity or withdrawal of consent. The prevalence of confirmed overall response among women with HRD-positive tumors — including those with and without BRCA mutations — who showed sensitivity to their last platinum-based therapy served as the study’s primary objective. Efficacy analyses also were conducted among all dosed patients with evaluable disease at baseline.
Median follow-up for OS was 12.2 months (IQR, 3.7-22.1).
Among all women who initiated treatment, 151 (33%) had platinum-resistant disease and 161 (35%) had platinum-refractory disease.
Results showed 13 of 47 women with platinum-sensitive, HRD-positive tumors naive to PARP inhibitors demonstrated overall response (27.65%; 95% CI, 15.6-42.6). These women had median PFS of 5.5 months (95% CI, 3.5-8.2) and median duration of response of 9.2 months (95% CI, 5.9 to not estimable), and 68% (95% CI, 53-81) achieved disease control.