medwireNews: ENGOT-OV16/NOVA trial results support the use of maintenance treatment with niraparib for platinum-sensitive recurrent ovarian cancer, in both patients with and without a germline (g)BRCA mutation.
The findings of this first ever phase III study of the oral poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP) 1/2 inhibitor in ovarian cancer were reported at the ESMO 2016 Congress in Copenhagen, Denmark, and simultaneously published online in The New England Journal of Medicine.
Progression-free survival (PFS) was significantly longer in women given the PARP 1/2 inhibitor than those given placebo, said presenting author Mansoor Raza Mirza, from Rigshospitalet–Copenhagen University Hospital.
For the 203 patients with a gBRCA mutation, median PFS was 21.0 months for the 138 patients randomly assigned to receive niraparib 300 mg/day versus 5.5 months for the 65 given placebo, with a significant hazard ratio (HR) of 0.27.
PARP 1/2 inhibitor benefit was also seen for 350 patients without gBRCA mutations who were given niraparib (n=234) versus those given placebo (n=116), with a PFS of 9.3 versus 3.9 months and a significant HR of 0.45.
And when patients without gBRCA alterations were stratified by homologous recombination deficiency (HRD) status, HRD-positive patients treated with niraparib and placebo had a median PFS of 12.9 and 3.8 months, respectively, and an HR of 0.38, again a significant difference. Among the gBRCA-negative, HRD-negative patients, the corresponding values were 6.9 versus 3.8 months, with a smaller but still significant HR of 0.58.
Overall survival data are not yet mature, the researchers say.
Haematological adverse event were the most common side effects, with any-grade thrombocytopenia, anaemia and neutropenia reported in 61.3%, 50.1% and 30.2% of niraparib-treated patients versus 5.6%, 6.7% and 6.1% of controls. Five patients given niraparib developed myelodysplastic syndrome, whereas there was one case of myelodysplastic syndrome and a second of acute myeloid leukaemia among the placebo-treated patients.
Grade 3 or 4 treatment emergent events occurred in 74.1% and 22.9% of the niraparib and placebo groups, with haematological side effects again the most common, but most patients remained on trial until progression.
And patient-reported outcomes and quality of life results were comparable in the treatment groups.
“These landmark results warrant niraparib maintenance treatment to the whole study population”, Mirza said.
Speaking at a press conference, Mirza told medwireNews that response to PARP inhibitors is linked to sensitivity to platinum-based chemotherapy but that does not rule out efficacy in platinum-resistant tumours and trials are ongoing.
“But I think that what we need now is to move upfront, to use this drug right after […] primary treatment and that’s what we are doing right now in trials”, he said.
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