Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial☆

Abstract

Background: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer. Patients and methods: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 Â 10 3 /ml received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.

Messenger RNA: A Technology of the Moment

“…10 This is because radiation-induced tumor necrosis is often delayed. [10][11][12] Once 4 to 6 weeks have elapsed, most of the inflammatory changes related to LRTs have resolved. However, inflammation and tumor persistence may be challenging to distinguish with imaging, as both usually appear as areas of arterial hyperenhancement on multiphase CT or MRI.…”

“…35 Ethiodized oil contains high amounts of iodine, which makes it intrinsically hyperdense on CT. As such, areas of arterial enhancement could be subtly obscured, limiting the accuracy of an evaluation of response. 12 However, the presence of ethiodized oil only minimally affects an MRI signal, so MRI use is advised to evaluate cTACE effectiveness. 12 The ethiodized oil-free embolotherapies, such as transarterial embolization and drug-eluting beads-TACE (DEB-TACE), can be evaluated equally with CT or MRI, 1,2 as there is no tumoral staining with hyperdense agents.…”

“…18 An HCC that has been completely treated with a radiation-based modality can retain arterial enhancement, which can be misinterpreted as viable disease by mRECIST and EASL. 12 If the LI-RADS response algorithm is employed, a persistent arterial enhancement is best classified as LR-TR equivocal or LR-TR not viable as long as the treated tumor is decreasing in size. 12 Inflammation secondary to immunotherapy can cause initial tumoral enlargement.…”

“…12 If the LI-RADS response algorithm is employed, a persistent arterial enhancement is best classified as LR-TR equivocal or LR-TR not viable as long as the treated tumor is decreasing in size. 12 Inflammation secondary to immunotherapy can cause initial tumoral enlargement. HCC-designed RC may misclassify this phenomena as progression, leading to unnecessary changes or cessation of therapy.…”

“…The combination produced better results than pegylated liposomal doxorubicin alone. 12 Unfortunately, the confirmatory PRO-CEED study had to be terminated at the interim analysis because the combination didn't meet the prespecified criteria for progression free survival. 13 Here they were trying to not only select for FRα but also for the heterogeneity that is seen across the different metastatic sites.…”