Detalle Publicación

NIRVANA-1: A multicentre randomized study comparing carboplatin-paclitaxel (CP) followed by niraparib (nira) to CP ebevacizumab (bev) followed by nira-bev in patients with FIGO stage III ovarian high-grade epithelial cancer and no residual disease after upfront surgery

Autores: Freyer, G.; González Martín, Antonio; Raspagliesi, F.; Peron, J.; Van Nieuwenhuysen, E.; Hasegawa, K.; Lim, M. C.; Ray-Coquard, I. L.
Título de la revista: ANNALS OF ONCOLOGY
ISSN: 0923-7534
Volumen: 33
Número: SUPPL 7
Páginas: S826
Fecha de publicación: 2022
Resumen:
Background A standard therapy for advanced high grade ovarian carcinoma (AHGOC) is an upfront complete surgery followed by adjuvant platinum-taxane chemotherapy adding maintenance targeted therapies. The most common maintenance strategies include bevacizumab and PARP inhibitors. Following the results of the PRIMA (Gonzales Martin, et al NEJM 2019) and PAOLA-1 (Ray-Coquard, et al NEJM 2019) studies, the question of the most efficient maintenance therapy for FIGO stage III patients remains uncertain considering PARPi alone or in combination with bev. Trial design NIRVANA-1 is an international randomized, open-label, phase II trial. 390 FIGO stage III patients with completely resected AHGOC, receive a first CP cycle and are randomized (1:1) to receive either 5 additional CP cycles followed by maintenance with nira or 5 cycles of CP + bev followed by maintenance with nira + bev. The total treatment duration will be 24 months for nira in both arms and 15 months for bev. Stratification factors include tumour BRCA status, FIGO stage (IIIA versus IIIB/IIIC) and use of hyperthermic intraperitoneal chemotherapy during surgery. The primary endpoint will be progression-free survival rate at 24 months. Secondary endpoints include safety, median PFS, PFS2, Time to First Subsequent Therapy (TFST), Time to Second Subsequent Therapy (TSST), OS, KELIM (K CA-125 ELIMination rate constant). The study is calibrated to detect a treatment effect corresponding to a 24-months PFS rate of 75% in the nira + bev arm and a 24-months PFS rate of 65% in the nira arm, translating in a HR of 0.67. The sample size is calculated to provide an 80% power to show a statistically significant PFS difference, accepting a 1-sided alpha risk of 10%, considering a minimal follow-up of 24 months, and dropout rate of 5%. The NIRVANA-1/GINECO-OV129b/ENGOT-ov63 trial is sponsored by the GINECO and currently recruiting in France, Spain, Italy, Belgium, Japan and Korea. The first patient was randomized in March 2022. Clinical trial identification NCT 05183984.
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