TY - JOUR
T1 - Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer
T2 - A randomized phase II study
AU - Brewer, Molly
AU - Angioli, Roberto
AU - Scambia, Giovanni
AU - Lorusso, Domenica
AU - Terranova, Corrado
AU - Panici, Pierluigi Benedetti
AU - Raspagliesi, Francesco
AU - Scollo, Paolo
AU - Plotti, Francessco
AU - Ferrandina, Gabriella
AU - Salutari, Vanda
AU - Ricci, Caterina
AU - Braly, Patricia
AU - Holloway, Robert
AU - Method, Michael
AU - Madiyalakan, Madi
AU - Bayever, Eliel
AU - Nicodemus, Christopher
N1 - Funding Information:
This study was funded by OncoQuest, Inc. Edmonton, Alberta. The authors acknowledge John Balser and Julie Wolfson of Veristat, Inc. Southboro Massachusetts for help with planning and conduct of the statistical analysis.
Publisher Copyright:
© 2019 Elsevier Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ygyno.2019.12.024
DO - 10.1016/j.ygyno.2019.12.024
M3 - Article
C2 - 31916979
AN - SCOPUS:85077364345
VL - 156
SP - 523
EP - 529
JO - Gynecologic Oncology
JF - Gynecologic Oncology
SN - 0090-8258
IS - 3
ER -