Neoadjuvant niraparib monotherapy produced tumor responses and enabled complete resection in selected patients with homologous recombination deficiency (HRD)-positive advanced ovarian cancer who were considered unlikely to achieve complete primary debulking surgery. Dan Liu, MD, and colleagues reported results from the phase II NANT trial conducted in China in The Lancet Oncology.
Neoadjuvant platinum-taxane chemotherapy followed by interval debulking surgery is the standard approach for patients with advanced ovarian cancer who are unlikely to achieve complete primary cytoreduction. NANT evaluated a chemotherapy-free neoadjuvant strategy using the poly(ADP-ribose) polymerase (PARP) inhibitor niraparib before surgery.
Study Details
The multicenter, single-arm phase II trial was conducted at six tertiary hospitals in China and enrolled 67 patients with treatment-naive, FIGO stage III or IV HRD-positive high-grade serous ovarian cancer. Patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and were considered unlikely to achieve complete primary debulking surgery based on prespecified criteria. BRCA1/2 mutations were identified in 29 patients (43%).
Patients received oral niraparib for two 28-day cycles at an individualized starting dose of 200 or 300 mg once daily. Those with complete or partial response or stable disease could proceed to interval debulking surgery, followed by standard postoperative platinum-based chemotherapy.
The coprimary endpoints were objective response rate among patients evaluable for response and the rate of R0 resection, defined as no gross residual disease, among those who underwent surgery.
Key Findings
Among 48 response-evaluable patients, 30 achieved a partial response, for an objective response rate of 63%. Another 12 patients had stable disease, resulting in a disease control rate of 88%.
Of the 40 patients who underwent interval debulking surgery, 32 achieved R0 resection, for an R0 resection rate of 80%.
In exploratory analyses, the objective response rate was 77% among patients with BRCA1/2 mutations and 50% among those with HRD-positive, BRCA wild-type disease. All six cases of progressive disease occurred in the BRCA wild-type subgroup. However, the investigators cautioned that these subgroup analyses were exploratory and based on small numbers.
Of the 40 patients who underwent surgery, 38 went on to receive platinum-based chemotherapy, and 30 subsequently received maintenance therapy.
Among the 48 response-evaluable patients, median progression-free survival was 19.7 months and median overall survival was 53.2 months. Median follow-up was 37.7 months. The investigators noted that because the study lacked a control group, the survival findings cannot establish a benefit over standard neoadjuvant chemotherapy.
Safety
Treatment-related adverse events of grade 3 or higher occurred in 61% of patients. The most common grade 3 or 4 events were thrombocytopenia in 48%, leukopenia in 19%, anemia in 18%, and neutropenia in 13%.
Dose interruptions were required in 52% of patients, dose reductions in 13%, and treatment discontinuation because of adverse events in 10%. Serious adverse events occurred in 19 patients (28%), most commonly thrombocytopenia in 15 (22%) and neutropenia in 3 (4%). No treatment-related deaths were reported.
“These findings do not show that neoadjuvant niraparib can replace platinum-taxane neoadjuvant chemotherapy,” the investigators wrote.
They said randomized trials are needed to compare the strategy directly with standard platinum-taxane neoadjuvant chemotherapy and better define patient selection.
Qinglei Gao, MD, of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, is the corresponding author.
DISCLOSURE: The study was funded by several Chinese national and provincial research programs and Zai Lab. The funders had no role in study design, data collection or analysis, data interpretation, or writing of the report. One author is an employee of Zai Lab and one is an employee of Precision Scientific; all other authors reported no competing interests.
