Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer: A randomized phase II study.
Adult
Aged
Antibodies, Monoclonal, Murine-Derived
/ administration & dosage
Antineoplastic Agents, Immunological
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Carboplatin
/ administration & dosage
Carcinoma, Ovarian Epithelial
/ drug therapy
Combined Modality Therapy
Female
Humans
Immunotherapy
/ methods
Middle Aged
Neoplasm Grading
Neoplasm Staging
Ovarian Neoplasms
/ drug therapy
Paclitaxel
/ administration & dosage
Treatment Outcome
Journal
Gynecologic oncology
ISSN: 1095-6859
Titre abrégé: Gynecol Oncol
Pays: United States
ID NLM: 0365304
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
11
11
2019
revised:
17
12
2019
accepted:
18
12
2019
pubmed:
10
1
2020
medline:
3
7
2020
entrez:
10
1
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31916979
pii: S0090-8258(19)31845-1
doi: 10.1016/j.ygyno.2019.12.024
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Murine-Derived
0
Antineoplastic Agents, Immunological
0
Carboplatin
BG3F62OND5
oregovomab
HX101E7L6S
Paclitaxel
P88XT4IS4D
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
523-529Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.