1. Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer: A randomized phase II study
- Author
-
Francessco Plotti, Giovanni Scambia, Gabriella Ferrandina, Christopher F. Nicodemus, Corrado Terranova, Vanda Salutari, Caterina Ricci, Patricia S. Braly, Paolo Scollo, Eliel Bayever, Francesco Raspagliesi, Michael W. Method, Robert W. Holloway, Pierluigi Benedetti Panici, Molly Brewer, Madi Madiyalakan, Roberto Angioli, and Domenica Lorusso
- Subjects
0301 basic medicine ,Oncology ,Adult ,medicine.medical_specialty ,Paclitaxel ,medicine.medical_treatment ,Phases of clinical research ,Carcinoma, Ovarian Epithelial ,Carboplatin ,03 medical and health sciences ,Antibodies, Monoclonal, Murine-Derived ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Oregovomab ,Median follow-up ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,Medicine ,Humans ,Progression-free survival ,Aged ,Neoplasm Staging ,Ovarian Neoplasms ,Chemotherapy ,business.industry ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,030104 developmental biology ,Treatment Outcome ,Settore MED/40 - GINECOLOGIA E OSTETRICIA ,Private practice ,030220 oncology & carcinogenesis ,Female ,Immunotherapy ,Neoplasm Grading ,INGLESE ,business ,Ovarian cancer ,medicine.drug - 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/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.
- Published
- 2020