Carol Aghajanian1, Virginia Filiaci2, Don S Dizon3, Jay W Carlson4, Matthew A Powell5, Angeles Alvarez Secord6, Krishnansu S Tewari7, David P Bender8, David M O'Malley9, Ashley Stuckey10, JianJiong Gao11, Fanny Dao12, Robert A Soslow13, Heather A Lankes14, Kathleen Moore15, Douglas A Levine12. 1. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, NY, United States. Electronic address: aghajanc@mskcc.org. 2. Department of Biostatics and Bioinformatics, Roswell Park Cancer Institute and NRG Oncology Buffalo Statistical and Data Management Center, Buffalo, NY, United States. 3. Lifespan Cancer Institute/Rhode Island Hospital, Providence, RI, United States. 4. Cancer Research for the Ozarks, Springfield, MO, United States. 5. Washington University, St. Louis, MO, United States. 6. Duke University, Durham, NC, United States. 7. University of California Irvine Medical Center, Orange, CA, United States. 8. University of Iowa, Iowa City, IA, United States. 9. Ohio State University Medical Center, James Cancer Center, Columbus, OH, United States. 10. Women and Infants Hospital, Providence, RI, United States. 11. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United States. 12. Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, United States. 13. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, NY, United States. 14. NRG Oncology Biospecimen Bank-Columbus, Biopathology Center, The Reseach Institue at Nationwide Children's Hospital, Columbus, OH, United States. 15. Stephenson Cancer Center and University of Oklahoma, Oklahoma City, OK, United States.
Abstract
OBJECTIVE:Paclitaxel and carboplatin (PC) is a standard initial therapy for advanced endometrial cancer. We evaluated the efficacy and tolerability of incorporating three novel agents into initial therapy. METHODS: In this randomized phase II trial, patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) endometrial cancer were randomly assigned to treatment with PC plus bevacizumab (Arm 1), PC plus temsirolimus (Arm 2) or ixabepilone and carboplatin (IC) plus bevacizumab (Arm 3). The primary endpoint was progression-free survival (PFS). Comparable patients on the PC Arm of trial GOG209 were used as historical controls. Secondary endpoints were response rate, overall survival (OS), and safety. RESULTS: Overall, 349 patients were randomized. PFS duration was not significantly increased in any experimental arm compared with historical controls (p > 0.039). Treatment HRs (92% CI) for Arms 1, 2, and 3 relative to controls were 0.81 (0.63-1.02), 1.22 (0.96-1.55) and 0.87 (0.68-1.11), respectively. Response rates were similar across arms (60%, 55% and 53%, respectively). Relative to controls, OS duration (with censoring at 36 months), was significantly increased in Arm 1 (p < 0.039) but not in Arms 2 and 3; the HRs (92% CIs) were 0.71 (0.55-0.91), 0.99 (0.78-1.26), and 0.97 (0.77-1.23), respectively. No new safety signals were identified. Common mutations and rates of mismatch repair protein loss are described by histotype. Potential predictive biomarkers for temsirolimus and bevacizumab were identified. CONCLUSION:PFS was not significantly increased in any experimental arm compared to historical controls. NRG Oncology/Gynecologic Oncology Group Study GOG-86P.
RCT Entities:
OBJECTIVE:Paclitaxel and carboplatin (PC) is a standard initial therapy for advanced endometrial cancer. We evaluated the efficacy and tolerability of incorporating three novel agents into initial therapy. METHODS: In this randomized phase II trial, patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) endometrial cancer were randomly assigned to treatment with PC plus bevacizumab (Arm 1), PC plus temsirolimus (Arm 2) or ixabepilone and carboplatin (IC) plus bevacizumab (Arm 3). The primary endpoint was progression-free survival (PFS). Comparable patients on the PC Arm of trial GOG209 were used as historical controls. Secondary endpoints were response rate, overall survival (OS), and safety. RESULTS: Overall, 349 patients were randomized. PFS duration was not significantly increased in any experimental arm compared with historical controls (p > 0.039). Treatment HRs (92% CI) for Arms 1, 2, and 3 relative to controls were 0.81 (0.63-1.02), 1.22 (0.96-1.55) and 0.87 (0.68-1.11), respectively. Response rates were similar across arms (60%, 55% and 53%, respectively). Relative to controls, OS duration (with censoring at 36 months), was significantly increased in Arm 1 (p < 0.039) but not in Arms 2 and 3; the HRs (92% CIs) were 0.71 (0.55-0.91), 0.99 (0.78-1.26), and 0.97 (0.77-1.23), respectively. No new safety signals were identified. Common mutations and rates of mismatch repair protein loss are described by histotype. Potential predictive biomarkers for temsirolimus and bevacizumab were identified. CONCLUSION: PFS was not significantly increased in any experimental arm compared to historical controls. NRG Oncology/Gynecologic Oncology Group Study GOG-86P.
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