| 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.
|
| MeSH term(s) |
Adjuvants, Immunologic/administration & dosage ; Adjuvants, Immunologic/adverse effects ; Adult ; Aged ; Aged, 80 and over ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/adverse effects ; Cancer Vaccines/immunology ; Carcinoma, Ovarian Epithelial/immunology ; Carcinoma, Ovarian Epithelial/pathology ; Carcinoma, Ovarian Epithelial/therapy ; Double-Blind Method ; Fallopian Tube Neoplasms/immunology ; Fallopian Tube Neoplasms/pathology ; Fallopian Tube Neoplasms/therapy ; Female ; Hemocyanins/administration & dosage ; Hemocyanins/immunology ; Humans ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms/immunology ; Ovarian Neoplasms/pathology ; Ovarian Neoplasms/therapy ; Peritoneal Neoplasms/immunology ; Peritoneal Neoplasms/pathology ; Peritoneal Neoplasms/therapy ; Vaccines, Conjugate/administration & dosage ; Vaccines, Conjugate/adverse effects ; Vaccines, Conjugate/immunology |
| Chemical Substances |
Adjuvants, Immunologic ; Cancer Vaccines ; Vaccines, Conjugate ; Hemocyanins (9013-72-3) ; keyhole-limpet hemocyanin (FV4Y0JO2CX) |
| Language |
English |
| Publishing date |
2019-10-22 |
| Publishing country |
United States |
| Document type |
Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural |
| ZDB-ID |
801461-9 |
| ISSN |
1095-6859 ; 0090-8258 |
| ISSN (online) |
1095-6859 |
| ISSN |
0090-8258 |
| DOI |
10.1016/j.ygyno.2019.09.015 |
| Database |
MEDical Literature Analysis and Retrieval System OnLINE |
