Roisin E O'Cearbhaill1, Wei Deng2, Lee-May Chen3, Joseph A Lucci4, Kian Behbakht5, Nick M Spirtos6, Carolyn Y Muller7, Benedict B Benigno8, Matthew A Powell9, Emily Berry10, Krishnansu S Tewari11, Parviz Hanjani12, Heather A Lankes13, Carol Aghajanian14, Paul J Sabbatini15. 1. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. Electronic address: ocearbhr@mskcc.org. 2. NRG Oncology Statistics & Data Management Center, Roswell Park Cancer Institute, Buffalo, NY, USA. Electronic address: wdeng@gogstats.org. 3. University of California San Francisco, San Francisco, CA, USA. Electronic address: lee-may.chen@ucsfmedctr.org. 4. The University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: Joseph.A.Lucci@uth.tmc.edu. 5. Rush University Medical Center, Chicago, IL, USA. Electronic address: kian.behbakht@ucdenver.edu. 6. Women's Cancer Center of Nevada, Las Vegas, NV, USA. Electronic address: nspirtos@wccenter.com. 7. Department of Obstetrics and Gynecology, University of New Mexico School of Medicine, Albuquerque, NM, USA. Electronic address: cmuller@salud.unm.edu. 8. University Gynecologic Oncology, Atlanta, GA, USA. Electronic address: benedict.benigno@ugynonc.com. 9. Washington University School of Medicine, St. Louis, MO, USA. Electronic address: powellm@wudosis.wustl.edu. 10. Northwestern Medicine Prentice Women's Hospital, Chicago, IL, USA. Electronic address: https://dremilyberry.com. 11. University of California Irvine Medical Center, Orange, CA, USA. Electronic address: ktewari@uci.edu. 12. Hanjani Institute for Gynecologic Oncology, Abington Memorial Hospital, Abington, PA, USA. Electronic address: phanjani@aol.com. 13. NRG Oncology, Operations Center-Philadelphia East, Philadelphia PA and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address: LankesH@NRGOncology.org. 14. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. Electronic address: aghajanc@mskcc.org. 15. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. Electronic address: sabbatip@mskcc.org.
Abstract
OBJECTIVE: Early-phase data have demonstrated induction of antibody responses to a polyvalent vaccine conjugate (Globo-H, GM2, MUC1-TN, TF) with adjuvant OPT-821. We sought to determine if this combination decreases the hazard of progression or death compared to OPT-821 alone in patients with ovarian cancer in second/third clinical complete remission following chemotherapy. Secondary and translational objectives were overall survival (OS), safety, and immunogenicity. METHODS: From 2010-2013, patients were randomized (1:1) to receive OPT-821±vaccine-KLH conjugate subcutaneously at weeks 1, 2, 3, 7, 11, and then every 12 weeks (total 11). Dose delay or reduction was not permitted. Patients were removed for pre-defined dose-limiting toxicity. RESULTS: Of 171 patients randomized, 170 were treated. Most had disease of serous histology (85%), stage 3 disease at diagnosis (77%), and had received 2 prior regimens (68%). 32% received >6 treatment cycles [median 6, each arm (p = 0.33)]. 77% discontinued due to progression, 4% due to toxicity, and 1 due to myeloid dysplastic syndrome (MDS). Maximum toxicities included grade 4 MDS and depression/personality change (1 each, unlikely related), as well as grade 3 gastrointestinal disorders and others (n = 21, 4 related). Lesser adverse events were injection site reactions (82%) and fever (11%). Estimated HR for progression-free survival (PFS) of the vaccine + OPT-821 to OPT-821 arm was 0.98 (95% CI: 0.71-1.36). At a median follow-up of 60 months, median OS was 47 and 46 months, respectively. CONCLUSIONS:Vaccine + OPT-821 compared to OPT-821 alone was modestly immunogenic and did not prolong PFS or OS. Multi-remission patients are a viable, well-defined population for exploring innovative consolidation and maintenance approaches. TRIAL REGISTRATION: NCT00857545.
RCT Entities:
OBJECTIVE: Early-phase data have demonstrated induction of antibody responses to a polyvalent vaccine conjugate (Globo-H, GM2, MUC1-TN, TF) with adjuvant OPT-821. We sought to determine if this combination decreases the hazard of progression or death compared to OPT-821 alone in patients with ovarian cancer in second/third clinical complete remission following chemotherapy. Secondary and translational objectives were overall survival (OS), safety, and immunogenicity. METHODS: From 2010-2013, patients were randomized (1:1) to receive OPT-821±vaccine-KLH conjugate subcutaneously at weeks 1, 2, 3, 7, 11, and then every 12 weeks (total 11). Dose delay or reduction was not permitted. Patients were removed for pre-defined dose-limiting toxicity. RESULTS: Of 171 patients randomized, 170 were treated. Most had disease of serous histology (85%), stage 3 disease at diagnosis (77%), and had received 2 prior regimens (68%). 32% received >6 treatment cycles [median 6, each arm (p = 0.33)]. 77% discontinued due to progression, 4% due to toxicity, and 1 due to myeloid dysplastic syndrome (MDS). Maximum toxicities included grade 4 MDS and depression/personality change (1 each, unlikely related), as well as grade 3 gastrointestinal disorders and others (n = 21, 4 related). Lesser adverse events were injection site reactions (82%) and fever (11%). Estimated HR for progression-free survival (PFS) of the vaccine + OPT-821 to OPT-821 arm was 0.98 (95% CI: 0.71-1.36). At a median follow-up of 60 months, median OS was 47 and 46 months, respectively. CONCLUSIONS: Vaccine + OPT-821 compared to OPT-821 alone was modestly immunogenic and did not prolong PFS or OS. Multi-remission patients are a viable, well-defined population for exploring innovative consolidation and maintenance approaches. TRIAL REGISTRATION: NCT00857545.
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