Molly Brewer1, Roberto Angioli2, Giovani Scambia3, Domenica Lorusso4, Corrado Terranova2, Pierluigi Benedetti Panici5, Francesco Raspagliesi6, Paolo Scollo7, Francessco Plotti2, Gabriella Ferrandina3, Vanda Salutari3, Caterina Ricci3, Patricia Braly8, Robert Holloway9, Michael Method10, Madi Madiyalakan11, Eliel Bayever11, Christopher Nicodemus12. 1. University of Connecticut School of Medicine, Farmington, CT, United States of America. Electronic address: mbrewer@uchc.edu. 2. Campus Biomedico of Rome, Rome, Italy. 3. Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy. 4. Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy; Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 5. Policlinico di Roma "Umberto I", Rome, Italy. 6. Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 7. Unita operative Ostetricia e Ginecologia, Dipartimento Materno Infantile Ospedale Cannizzario di Catania, Catania, Italy. 8. Womens Cancer Care, Covington, LA, United States of America. 9. AdventHealth Cancer, Orlando, FL, United States of America. 10. Michiana Hematology Oncology, South Bend, IN, United States of America. 11. OncoQuest Inc., Edmonton, Alberta, Canada. 12. AIT Strategies, Franconia, NH, United States of America.
Abstract
BACKGROUND: This randomized phase II study tested the hypothesis that schedule dependent chemo-immunotherapy with oregovomab improves progression free survival (PFS) and overall survival (OS) in optimally resected, Stage III/IV ovarian cancer. METHODS:Patients from both academic centers and private practice in the US and Italy with Stage III/IVoptimally cytoreduced ovarian cancer were randomized to standard six cycle IV carboplatin-paclitaxel chemotherapy (CP) versus CP plus four immunizations with oregovomab (CPO). A translational assessment of a cellular immune response was the primary endpoint; PFS and OS were measured as secondary endpoints. FINDINGS:97 patients at thirteen centers were accrued to the protocol, 47 to CPO and 50 to CP. Technical issues led to inconsistent performance of the primary CA125 ELISPOT leading to unevaluable results. At a median follow up of 42 months, PFS and OS outcomes revealed an unexpectedly large treatment effect for CPO relative to CP alone, with median PFS of 41.8 months (95% C.I.: 21.8 - N.E.) for CPO and 12.2 months (10.4-18.6) for CP (p = 0.0027, HR 0.46, CI 0.28-0.7). For OS, the median for CPO has not yet been reached (NE) (45.2-NE) and for CP was 43.2 months (31.8-NE) (p = 0.043, HR 0.35, CI 0.16-0.74). The oregovomab treatment resulted in no change in toxicity profile from CP. INTERPRETATION: The previously identified potential clinical benefit of IV CP when administered with oregovomab was further refined in this randomized phase II study. Increases of PFS and OS of statistically and clinically significant magnitude were evident in this study of a front line chemo-immunotherapy treatment of ovarian cancer.
RCT Entities:
BACKGROUND: This randomized phase II study tested the hypothesis that schedule dependent chemo-immunotherapy with oregovomab improves progression free survival (PFS) and overall survival (OS) in optimally resected, Stage III/IV ovarian cancer. METHODS:Patients from both academic centers and private practice in the US and Italy with Stage III/IV optimally cytoreduced ovarian cancer were randomized to standard six cycle IV carboplatin-paclitaxel chemotherapy (CP) versus CP plus four immunizations with oregovomab (CPO). A translational assessment of a cellular immune response was the primary endpoint; PFS and OS were measured as secondary endpoints. FINDINGS: 97 patients at thirteen centers were accrued to the protocol, 47 to CPO and 50 to CP. Technical issues led to inconsistent performance of the primary CA125 ELISPOT leading to unevaluable results. At a median follow up of 42 months, PFS and OS outcomes revealed an unexpectedly large treatment effect for CPO relative to CP alone, with median PFS of 41.8 months (95% C.I.: 21.8 - N.E.) for CPO and 12.2 months (10.4-18.6) for CP (p = 0.0027, HR 0.46, CI 0.28-0.7). For OS, the median for CPO has not yet been reached (NE) (45.2-NE) and for CP was 43.2 months (31.8-NE) (p = 0.043, HR 0.35, CI 0.16-0.74). The oregovomab treatment resulted in no change in toxicity profile from CP. INTERPRETATION: The previously identified potential clinical benefit of IV CP when administered with oregovomab was further refined in this randomized phase II study. Increases of PFS and OS of statistically and clinically significant magnitude were evident in this study of a front line chemo-immunotherapy treatment of ovarian cancer.
Authors: Kimberly Fung; Sai Kiran Sharma; Outi Keinänen; Kara Long Roche; Jason S Lewis; Brian M Zeglis Journal: Mol Pharm Date: 2020-07-16 Impact factor: 4.939
Authors: Maximilian N Kinzler; Falko Schulze; Steffen Gretser; Nada Abedin; Jörg Trojan; Stefan Zeuzem; Andreas A Schnitzbauer; Dirk Walter; Peter J Wild; Katrin Bankov Journal: Cancers (Basel) Date: 2022-09-27 Impact factor: 6.575