Carboplatin/pegylated liposomal Doxorubicin/Bevacizumab (CD-BEV) vs. Carboplatin/Gemcitabine/Bevacizumab (CG-BEV) in patients with recurrent ovaria...

Date 19 October 2018
Event ESMO 2018 Congress
Session Proffered paper session - Gynaecological cancers
Topics Ovarian Cancer
Anticancer Agents
Presenter Jacobus Pfisterer
Citation Annals of Oncology (2018) 29 (suppl_8): viii332-viii358. 10.1093/annonc/mdy285
Authors J. Pfisterer1, A.P. Dean2, K. Baumann3, J. Rau4, P. Harter5, F. Joly6, J. Sehouli7, U. Canzler8, B. Schmalfeldt9, C. Shannon10, A. Hein11, D.U. Reimer12, L.C. Hanker13, T. Petit14, F. Marmé15, A. El-Balat16, R. Glasspool17, N. de Gregorio18, S. Mahner19, J. Kurtz20
  • 1Gyn Onc, AGO Study Group & Gynecologic Oncology Center, 24103 - Kiel/DE
  • 2Gynaecological Oncology, AGO Study Group & St. John of God Hospital, 6008 - Subiaco/AU
  • 3Gynaecology, AGO Study Group & Klinikum der Stadt Ludwigshafen am Rhein gGmbH, 67063 - Ludwigshafen/DE
  • 4Coordinating Centre For Clinical Trial, AGO Study Group & Coordinatoring Center for Clinical Trials Philipps-University of Marburg, 35043 - Marburg/DE
  • 5Gynecology & Gynecologic Oncology, AGO Study Group & Kliniken Essen Mitte Evang. Huyssens-Stiftung, 45136 - Essen/DE
  • 6Gynaecology, GINECO & Centre Francois Baclesse Caen, 14000 - Caen/FR
  • 7Gynaecology, AGO Study Group & Department of Gynecology, Charité, Campus-Virchow-Klinikum, 13353 - Berlin/DE
  • 8Gynaecology, AGO Study Group & Medical Faculty and University Hospital Carl Gustav Carus, Technical University Dresden, 01307 - Dresden/DE
  • 9Gynaecology, AGO Study Group & Technical University of Munich - Klinikum rechts der Isar; current address: University of Medical Center Hamburg-Eppendorf, 20246 - Hamburg/DE
  • 10Oncology Department, ANZGOG & Mater Cancer Care Centre, 4101 - Brisbane/AU
  • 11Gynaecology, AGO Study Group & Erlangen University Hospital, 91054 - Erlangen/DE
  • 12Gynaecology, AGO Austria & Innsbruck Medical University, 6020 - Innsbruck/AT
  • 13Gynaecology, AGO Study Group & University Hospital Schleswig-Holstein, Campus Lübeck, 23562 - Lübeck/DE
  • 14Gynaecology, GINECO & Paul Strauss Cancer Center and University of Strasbourg, 67065 - Strasbourg/FR
  • 15Gynaecology, AGO Study Group & National Center for Tumor disease, University of Heidelberg, 69120 - Heidelberg/DE
  • 16Gynaecology, AGO Study Group & University Hospital Frankfurt, 60590 - Frankfurt/DE
  • 17Gynaecology, AGO Study Group & Beatson West of Scotland Cancer Centre, G12 0YN - Glasgow/GB
  • 18Gynaecology, AGO Study Group & University of Ulm, 89075 - Ulm/DE
  • 19Gynaecology, AGO Study Group & University Medical Center Hamburg-Eppendorf and University of Munich, Ludwig-Maximilians-University Munich,; current address University of Munich, 81377 - Munich/DE
  • 20Haematology-oncology, GINECO & CHRU de Strasbourg Hôpital Civil, 67000 - Strasbourg/FR

Abstract

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.

Clinical trial identification

Legal entity responsible for the study

AGO Research GmbH.

Funding

Hoffmann La Roche.

Editorial Acknowledgement

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.