Independent radiologic review: bevacizumab in combination with gemcitabine and carboplatin in recurrent ovarian cancer

Carol Aghajanian; Barbara Goff; Lawrence R Nycum; Yan Wang; Amreen Husain; Stephanie Blank

doi:10.1016/j.ygyno.2014.02.003

Independent radiologic review: bevacizumab in combination with gemcitabine and carboplatin in recurrent ovarian cancer

Gynecol Oncol. 2014 Apr;133(1):105-10. doi: 10.1016/j.ygyno.2014.02.003. Epub 2014 Feb 6.

Authors

Carol Aghajanian¹, Barbara Goff², Lawrence R Nycum³, Yan Wang⁴, Amreen Husain⁴, Stephanie Blank⁵

Affiliations

¹ Memorial Sloan-Kettering Cancer Center, Gynecologic Medical Oncology Service, 300 East 66th Street, New York, NY 10065, USA; Weill Cornell Medical College, 445 East 69th Street, New York, NY 10021, USA. Electronic address: aghajanc@mskcc.org.
² University of Washington School of Medicine, Department of Obstetrics and Gynecology, Box 356460, Seattle, WA 98195, USA.
³ Novant Health Forsyth Medical Center, Division of Gynecologic Oncology, 3333 Silas Creek Pkwy, Winston-Salem, NC 27103, USA.
⁴ Genentech, Inc., Product Development, 1 DNA Way, South San Francisco, CA 94080, USA.
⁵ New York University School of Medicine, Department of Obstetrics and Gynecology, 160 East 34th Street, New York, NY 10016, USA.

PMID: 24508841
DOI: 10.1016/j.ygyno.2014.02.003

Abstract

Objective: OCEANS, a randomized, placebo-controlled, phase III trial, found that adding bevacizumab to gemcitabine-carboplatin (GC) significantly improved investigator-determined progression-free survival (PFS) and objective response rate (ORR) in platinum-sensitive, recurrent ovarian cancer. To evaluate the reliability of assessment of progression and objective response per RECIST, radiologic and clinical data were assessed by an independent review committee (IRC).

Methods: Radiologic images and clinical data were provided prospectively to the IRC for all randomized patients (N=484). Data were reviewed in a blinded fashion per RECIST (modified v1.0). PFS and ORR were analyzed based on the IRC assessment. Concordance between investigator- and IRC-assessed progression and objective response was assessed.

Results: The IRC analysis demonstrated a statistically significant increase in PFS (hazard ratio [HR]=0.451; 95% confidence interval [CI]=0.351 to 0.580, p<0.0001) consistent with the benefit reported by investigators (HR=0.484; 95% CI=0.388 to 0.605, p<0.0001). The concordance rate, defined by agreement on progression status, was 74.2% overall, and comparable between treatment arms (bevacizumab, 75.2% vs. placebo, 73.1%). IRC-assessed ORR was significantly improved with bevacizumab (bevacizumab, 74.8% vs. placebo, 53.7%; p<0.0001), consistent with the investigator-assessed results. The concordance rate for objective response was 79.8% overall, and comparable between treatment arms (bevacizumab, 78.9% vs. placebo, 80.6%).

Conclusions: IRC-determined results were highly consistent with those determined by investigators, demonstrating that bevacizumab plus GC provides a significant improvement in PFS and ORR. These results suggest that investigators can reliably assess disease progression and objective response in recurrent ovarian cancer using RECIST, without the necessity of a full IRC review.

Keywords: Bevacizumab; IRC; Independent review; Phase 3; Recurrent ovarian cancer.

Publication types

Clinical Trial, Phase III
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Advisory Committees*
Aged
Antibodies, Monoclonal, Humanized / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Bevacizumab
Carboplatin / administration & dosage
Deoxycytidine / administration & dosage
Deoxycytidine / analogs & derivatives
Disease-Free Survival
Female
Gemcitabine
Humans
Middle Aged
Neoplasm Recurrence, Local / diagnostic imaging*
Neoplasm Recurrence, Local / drug therapy
Ovarian Neoplasms / diagnostic imaging*
Ovarian Neoplasms / drug therapy
Radiology / standards*
Tomography, X-Ray Computed

Substances

Antibodies, Monoclonal, Humanized
Deoxycytidine
Bevacizumab
Carboplatin
Gemcitabine