2019 ASCO Annual Meeting!
Session: Gynecologic Cancer
Type: Oral Abstract Session
Time: Monday June 3, 1:15 PM to 4:15 PM
Combination of niraparib and bevacizumab versus niraparib alone as treatment of recurrent platinum-sensitive ovarian cancer: A randomized controlled chemotherapy-free study—NSGO-AVANOVA2/ENGOT-OV24.
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 5505)
Author(s): Mansoor Raza Mirza, Elisabeth Avall-Lundqvist, Michael J. Birrer, Rene dePont Christensen, Gitte-Bettina Nyvang, Susanne Malander, Maarit Anttila, Theresa Louise Werner, Bente Lund, Gabriel Lindahl, Sakari Hietanen, Ulla Peen, Maria Dimoula, Henrik Roed, Anja Ør Knudsen, Louisa Boufercha, Synnove Staff, Anders Krog Vistisen, Line Bjørge, Johanna Unelma Maenpaa; NSGO and Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark; Linkoping University Hospital, Linkoping, Sweden; The University of Alabama at Birmingham, Birmingham, AL; Research Unit of General Practice, Institute of Public Health, University of Southern Denmark, Odense, Denmark; Odense Universitetshospital, Odense, Denmark; Nordic Society of Gynecologic Oncology (NSGO) and Lund University Hospital, Lund, Sweden; NSGO and Kuopio University Hospital, Kuopio, Finland; University of Utah, Salt Lake City, UT; Aalborg Hospital, Aalborg, Denmark; Linkoping University Hospital, Linköping, Sweden; Turku University Hospital, Turku, Finland; University Hospital of Herev, Rungsted, Denmark; Sahlgrenska University Hospital, Göteborg, Sweden; Department of Oncology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; University Hospital Odense, Odense, Denmark; Rigshospitalet, Copenhagen, Denmark; Tampere University Hospital, Tampere, Finland; Haukeland University Hospital, Bergen, Norway; NSGO and Tampere University Hospital, Department of Obstetrics and Gynecology, Tampere, Finland
Background: Standard treatment of platinum-sensitive recurrent ovarian cancer (PSROC) is platinum based combination chemotherapy ± bevacizumab. However, this treatment modality is hardly curative, and is associated with significant toxicity. Both bevacizumab (BEV) and PARP inhibitors (PARPi) have demonstrated efficacy in PSROC. There is preclinical evidence of enhanced activity of the combination. This is the proof-of-concept randomized trial of PARPi-BEV combination against PARPi monotherapy as treatment in PSROC, regardless of number of previous lines of therapies. Methods: In this randomized, open-label, phase 2 study, women with measurable/evaluable, high-grade serous or endometrioid PSROC were randomized to niraparib 300mg once daily or the combination of niraparib 300mg once daily and BEV 15mg/kg IV every 3 weeks until disease progression (1:1 randomization). The primary endpoint was progression-free survival (PFS). Stratification was according to homologous recombination-deficiency(HRD) status (MyChoice HRD) and chemotherapy-free-interval (CFI)(6-12months (mo) vs. >12mo). First-line maintenance bevacizumab was permitted. Results: Of 97 enrolled patients, 48 were randomized to niraparib monotherapy and 49 to the chemotherapy-free combination. The combined treatment significantly improved PFS compared to niraparib alone: median 11.9 vs. 5.5 mo; hazard ratio (HR) adjusted for stratification factors 0.35; 95% confidence interval (CI),[0.21 to 0.57]; P<0.001. Pre-planned exploratory subgroup analyses: patients with HRD-positive tumors (n=54) HR 0.36 (CI, 0.18-0.69); HRD-negative disease (n=43) HR, 0.47 (CI, 0.24-0.95); gBRCAmut patients (n=34) HR 0.53 (CI, 0.23-1.21); non-gBRCAmut patients (n=63) HR 0.33; CI, 0.18-0.61); CFI of 6 to 12 mo (n=38) HR, 0.29 (CI, 0.14 to 0.62); CFI of ≥12 mo (n=59) HR, 0.42; (CI, 0.22 to 0.80). There was no difference in treatment-emergent grade 3-4 adverse events except for the rate of hypertension (26.5% vs. 0%) and neutropenia (12.2% vs. 2.1%). Patient-reported outcomes measured using EORTC QLQ-C30 and OV28 were similar for both treatment arms. Conclusions: Both niraparib alone and the combination had meaningful activity in PSROC. Compared to niraparib alone, the chemotherapy-free regimen of niraparib and BEV significantly improved PFS in women with PSROC,regardless of HRD status and duration of CFI. Clinical trial information: NCT02354131