Carol Aghajanian1, Barbara Goff2, Lawrence R Nycum3, Yan Wang4, Amreen Husain4, Stephanie Blank5. 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.
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.
RCT Entities:
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.
Authors: Carol Aghajanian; Barbara Goff; Lawrence R Nycum; Yan V Wang; Amreen Husain; Stephanie V Blank Journal: Gynecol Oncol Date: 2015-08-10 Impact factor: 5.482
Authors: Gerald Falchook; Robert L Coleman; Andrzej Roszak; Kian Behbakht; Ursula Matulonis; Isabelle Ray-Coquard; Piotr Sawrycki; Linda R Duska; William Tew; Sharad Ghamande; Anne Lesoin; Peter E Schwartz; Joseph Buscema; Michel Fabbro; Alain Lortholary; Barbara Goff; Razelle Kurzrock; Lainie P Martin; Heidi J Gray; Siqing Fu; Emily Sheldon-Waniga; Huamao Mark Lin; Karthik Venkatakrishnan; Xiaofei Zhou; E Jane Leonard; Russell J Schilder Journal: JAMA Oncol Date: 2019-01-10 Impact factor: 31.777
Authors: Abolfazl Zargari; Yue Du; Morteza Heidari; Theresa C Thai; Camille C Gunderson; Kathleen Moore; Robert S Mannel; Hong Liu; Bin Zheng; Yuchen Qiu Journal: Phys Med Biol Date: 2018-08-06 Impact factor: 3.609