Carboplatin/Pegylated Liposomal Doxorubicin/Bevacizumab (CD-Bev) vs. Carboplatin/Gemcitabine/Bevacizumab (CG-BEV) in Patients with Recurrent Ovarian Cancer: a Prospective Randomized Phase iii Engot/GCiG-Intergroup Study (Ago Study Group, Ago-AUSTRiA, ANZGOG,GiNECO, SGCTG)

Background: In patients with recurrent ovarian cancer (ROC) suitable for platinum-based retreatment (PBT), standard includes CG-BEV and Carboplatin(C)/pegylated-liposomal- Doxorubicin (D). CG-BEV significantly increases progression-free-survival (PFS) over CG alone whilst CD has one of the best therapeutic indices for ROC-PBT. The aim of this trial was to evaluate whether CD is superior to CG when given in combination with BEV with investigator-determined PFS as primary objective (NCT01837251). Methods: Between 2013/08 and 2015/07 682 pts. with ROC-PBT were randomized to standard CG-BEV (n = 337) or experimental CD-BEV (n = 345). Secondary objectives were overall survival (OS), biological progression-free survival (PFSBIO) by serum CA125, quality of life (QoL) assessed by EORTC-QLQ-C30 and QLQ-OV28, safety and tolerability. The trial was designed to have 80% power (two-sided logrank-test, alpha level 5%) to show a 26.6% change in PFS (Hazard Ratio (HR) 0.79; 564 PFS events). Results: At data cut-off 571 events occurred. Mean age was 61.1 (SD 10.3) years, 87.4% had serous histology, 83.1% were high grade, 41.5% were pretreated with BEV as part of first-line treatment. CG-BEV was associated with 359 (53,3%) serious adverse events vs. 314 (46,7%) for CD-BEV (p = 0.083). Median PFS in the standard arm CG-BEV was 11.7 months (95% CI 11.1-12.8) vs. 13.3 months (95% CI 11.7-14.3) in the experimental arm CD-BEV (HR 0.80; 95% CI 0.68-0.96, p = 0.0128). In the stratum with previous anti-angiogenic treatment (N = 309) median PFS was 10.1 months (95% CI 8.5-11.2) for CG-BEV vs. 11.3 months (95% CI 10.1-13.8) for CD-BEV (HR 0.73; 95% CI 0.57-0.94, p = 0.0126). Conclusions: CD-BEV provided a significant PFS improvement compared to CG-BEV in patients with ROC suitable for PBT. A significant PFS improvement was also seen in the subgroup of patients with previous anti-angiogenic treatment. CD-BEV was associated with fewer serious adverse events. Thus CD-BEV might be an important addition to the therapeutic options in these patients. Legal entity responsible for the study: AGO Research GmbH. Funding: Hoffmann La Roche. Disclosure: J. Pfisterer: Consulting or Advisory role: Roche; Research funding: Roche; Travel, Accomodations, Expenses: Roche. A.P. Dean: Honoraria: Baxalta, Astra Zeneca; Consulting or Advisory role: Baxalta, specialized Therapeutics; Speakers' bureau: Baxalta; Travel, Accomodations, Expenses: Amgen. P. Harter: Consulting or Advisory role: AstraZeneca, Roche/Genentech, Tesaro, Clovis, PharmaMar, Lilly, Sotio; Travel, Accommodations, Expenses: Medac. F. Joly: Consulting or Advisory role: Roche, Janssen; Travel, Accomodations, Expenses: Roche, Janssen. J. Sehouli: Honoraria: Roche, AstraZeneca, Tesaro, PharmaMar; Consulting or Advisory role: Clovis, Roche, AstraZeneca, Tesaro, Novartis; Research funding: Amgen, Novartis, Lilly, Bayer. U. Canzler: Honoraria: AstraZeneca, Roche Consulting or Advisory role: Roche. B. Schmalfeldt: Consulting or Advisory role: Roche, AstraZeneca, Tesaro; Travel, Accomodations, Expenses: Roche, AstraZeneca. C. Shannon: Consulting or Advisory role: AstraZeneca, Roche. D.U. Reimer: Consulting or Advisory role: AstraZeneca, PharmaMar; Travel, Accomodations, Expenses: AstraZeneca, Amgen, PharmaMar, Roche Patents, Royalties, other intellectual property: yes. L.C. Hanker: Consulting or Advisory role: Roche, Tesaro; Travel, Accomodations, Expenses: Roche, AstraZeneca. T. Petit: Consulting or Advisory role: Roche, Pfizer; Travel, Accomodations, Expenses: Roche, Pierre Fabre. F. Marme´: Honoraria: Roche, Amgen, AstraZeneca, Eisai, Celgene, Novartis, Pfizer, Genomic Health; Consulting or Advisory Role: roche, AstraZeneca, Novartis; Travel, Accomodations, Expenses: Roche, Amgen, AstraZeneca, Eisai, Celgene, Novartis, Pfizer, PharmaMar. A. El-Balat: Honoraria: Roche, AstraZeneca, Tesaro; Consulting or Advisory role: Roche, AstraZeneca, PharmaMar; Travel, Accomodations, Expenses: PharmaMar, Tesaro, Clovis. R. Glasspool: Consulting or Advisory role: Tesaro, Roche, Clovis Oncology, Clovis; Research Funding: Ignyta, Boehringer Ingelheim, Roche; Travel, Accomodations, Expenses: AstraZeneca, Roche, Tesaro. N. de Gregorio: Consulting or Advisory role: Roche, AstraZeneca, Tesaro; Travel, Accomodations, Expenses: Tesaro. S. Mahner: Honoraria: Roche/Genentech, AstraZeneca, PharmaMar, Medac, Jenapharm, Janssen-Cilag, Teva, GlaxoSmithKline; Consulting or Advisory role: Roche, AstraZeneca, Merck Sharp & Dohme, Janssen-Cilag, Tesaro, Medac; Research funding: Roche, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Janssen-Cilag, Medac, PharmaMar, Tesaro, Bayer. J-E. Kurtz: Consulting or Advisory role: Tesaro, AstraZeneca; Travel, Accomodations, Expenses: Roche, PharmaMar. All other authors have declared no conflicts of interest.