Anne Floquet1, Ignace Vergote2, Nicoletta Colombo3, Bent Fiane4, Bradley J Monk5, Alexander Reinthaller6, Paula Calvert7, Thomas J Herzog8, Werner Meier9, Jae-Weon Kim10, Josep M del Campo11, Michael Friedlander12, Carmela Pisano13, Seiji Isonishi14, Rocco J Crescenzo15, Catherine Barrett16, Karrie Wang15, Ionel Mitrica15, Andreas du Bois17. 1. Institut Bergonié, Bordeaux, France. 2. University Hospitals Leuven, Dept. of Gynaecological Oncology, Leuven, Belgium. 3. University of Milan Bicocca and European Institute of Oncology, Gynecologic Oncology, Milan, Italy. 4. Department of Gynecology and Gynecologic Oncology, Stavanger University Hospital, Stavanger, Norway. 5. Creighton University School of Medicine at St. Joseph's Hospital and Medical Center, Division of Gynecologic Oncology, Phoenix, AZ, USA. 6. Allgemeines Krankenhaus Wien, Dept. Gynecology and Obstetrics, Vienna, Austria. 7. All-Ireland Co-operative Oncology Group, Dublin, Ireland. 8. University of Cincinnati Cancer Institute, Cincinnati, OH, USA. 9. Evangelisches Krankenhaus Düsseldorf, Düsseldorf, Germany. 10. Department of Obstetrics and Gynecology, Seoul National University, Seoul, Republic of Korea. 11. Vall d'Hebron University Hospital, Dept. of Medical Oncology, Barcelona, Spain. 12. The Prince of Wales Cancer Center, Dept. of Medical Oncology, Randwick, NSW, Australia. 13. Department of Uro-gynecologic Oncology, Istituto Nazionale Tumori Fondazione G Pascale-IRCCS, Naples, Italy. 14. Department of Obstetrics and Gynecology, Jikei University School of Medicine, Daisan Hospital, Tokyo, Japan. 15. GlaxoSmithKline, Collegeville, PA, USA. 16. GlaxoSmithKline Pharmaceuticals, Uxbridge, United Kingdom. 17. Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany. Electronic address: prof.dubois@googlemail.com.
Abstract
BACKGROUND: Analysis of progression-free survival (PFS) as the primary endpoint in advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer (AEOC) trials may be confounded by the difficulty of radiologic evaluation of disease progression and the potential for discrepancy between investigator and blinded independent central assessments. PFS as assessed by local investigator (INV) was the primary endpoint of AGO-OVAR16, a randomized, double-blind trial of pazopanib maintenance therapy in AEOC. To confirm the robustness of the primary analysis, PFS was also evaluated by blinded independent central review (BICR). METHODS:Patients with histologically confirmed AEOC (N = 940) were randomized 1:1 to receive pazopanib 800 mg/day or placebo for up to 24 months. Tumor response in the intent-to-treat population was evaluated by CT/MRI every 6 months and analyzed per RECIST 1.0. RESULTS:Pazopanib prolonged PFS versus placebo by INV (median 17.9 vs 12.3 months; hazard ratio [HR] = 0.766, 95% confidence interval [CI]: 0.643-0.911; P = 0.0021). Results for PFS by BICR were similar (median 15.4 vs 11.8 months; HR = 0.802, 95% CI: 0.678-0.949; P = 0.0084). Progression events were recorded later by INV in 23% of pazopanib-treated patients and 17% of placebo-treated patients. The overall concordance between INV and BICR assessments was 84% and 86% in the pazopanib and placebo arms, respectively. CONCLUSIONS: By INV and BICR assessments, maintenance therapy with pazopanib in AEOC provided a significantly longer PFS than placebo. The good overall concordance between INV and BICR assessments, as well as HR and P value consistency, supports the reliability of investigator-assessed PFS as the primary endpoint in AGO-OVAR16.
RCT Entities:
BACKGROUND: Analysis of progression-free survival (PFS) as the primary endpoint in advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer (AEOC) trials may be confounded by the difficulty of radiologic evaluation of disease progression and the potential for discrepancy between investigator and blinded independent central assessments. PFS as assessed by local investigator (INV) was the primary endpoint of AGO-OVAR16, a randomized, double-blind trial of pazopanib maintenance therapy in AEOC. To confirm the robustness of the primary analysis, PFS was also evaluated by blinded independent central review (BICR). METHODS:Patients with histologically confirmed AEOC (N = 940) were randomized 1:1 to receive pazopanib 800 mg/day or placebo for up to 24 months. Tumor response in the intent-to-treat population was evaluated by CT/MRI every 6 months and analyzed per RECIST 1.0. RESULTS:Pazopanib prolonged PFS versus placebo by INV (median 17.9 vs 12.3 months; hazard ratio [HR] = 0.766, 95% confidence interval [CI]: 0.643-0.911; P = 0.0021). Results for PFS by BICR were similar (median 15.4 vs 11.8 months; HR = 0.802, 95% CI: 0.678-0.949; P = 0.0084). Progression events were recorded later by INV in 23% of pazopanib-treated patients and 17% of placebo-treated patients. The overall concordance between INV and BICR assessments was 84% and 86% in the pazopanib and placebo arms, respectively. CONCLUSIONS: By INV and BICR assessments, maintenance therapy with pazopanib in AEOC provided a significantly longer PFS than placebo. The good overall concordance between INV and BICR assessments, as well as HR and P value consistency, supports the reliability of investigator-assessed PFS as the primary endpoint in AGO-OVAR16.
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