Long-term outcomes of patients with recurrent ovarian cancer treated with a polyvalent vaccine with bevacizumab combination Journal Article
| Authors: | Kahn, R. M.; Ragupathi, G.; Zhou, Q. C.; Iasonos, A.; Kravetz, S.; Hensley, M. L.; Konner, J. A.; Makker, V.; Tew, W. P.; Aghajanian, C.; Sabbatini, P. J.; O’Cearbhaill, R. E. |
| Article Title: | Long-term outcomes of patients with recurrent ovarian cancer treated with a polyvalent vaccine with bevacizumab combination |
| Abstract: | Background: To characterize the safety, immunogenicity, and outcomes of patients with high-grade serous ovarian cancer (HGSOC) in second or greater remission treated with a polyvalent antigen-KLH plus OPT-821 vaccine construct and bevacizumab. Methods: Patients with recurrent HGSOC were treated with the vaccine plus bevacizumab at our institution from 01/05/2011 to 03/20/2012. Follow-up continued until 03/2021. Blood/urine samples were collected. “Responders” had an immunogenic response to ≥ 3 antigens; “non-responders” to ≤ 2 antigens. Results: Twenty-one patients were treated on study. One developed a dose-limiting toxicity (grade 4 fever). Two (10%) experienced bevacizumab-related grade 3 hypertension. Thirteen (68%) and 16 (84%) of 19 responded to ≥ 3 and ≥ 2 antigens, respectively (Globo-H, GM2, TF cluster Tn, MUC-1). Four of 21 patients were alive > 5 years post-treatment. Responders and non-responders had a median PFS of 4.9 months (95% CI: 2.8–8.1) and 5.0 months (95% CI: 0.7-cannot estimate), respectively; median OS was 30.7 months (95% CI: 16.9–52.0) and 34.2 months (95% CI: 12.8-cannot estimate), respectively. On two-timepoint analysis (baseline, week 17), increased IL-8 exhibited improved PFS (HR as 10-unit increase, 0.43; p = 0.04); increased PDGF exhibited worse OS (HR as 10-unit increase, 1.01; p = 0.02). Conclusions: This is the longest follow-up of vaccine administration with bevacizumab in patients with ovarian cancer. The vaccine was well tolerated with bevacizumab. Response was not associated with improved survival. On two-timepoint analysis, increased IL-8 was associated with significant improvement in PFS; increased PDGF with significantly worse OS. For all timepoint measurements, cytokine levels were not significantly associated with survival. Trial registration: NCT01223235. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. |
| Keywords: | platelet derived growth factor; adult; cancer survival; clinical article; treatment response; aged; cancer surgery; unclassified drug; overall survival; fatigue; cancer recurrence; bevacizumab; doxorubicin; cancer combination chemotherapy; drug safety; hypertension; gemcitabine; cancer patient; topotecan; follow up; antineoplastic agent; cancer diagnosis; ovarian cancer; cytoreductive surgery; ovarian neoplasms; protein blood level; computer assisted tomography; neoplasm recurrence, local; antineoplastic combined chemotherapy protocols; myalgia; interleukin 8; creatinine; cyclophosphamide; creatinine blood level; brca1 protein; brca2 protein; enzyme linked immunosorbent assay; fever; injection site reaction; fibroblast growth factor 2; alkaline phosphatase; bilirubin; cytokines; karnofsky performance status; immune response; immunotherapy; interleukin-8; cancer vaccine; tumor recurrence; ovary tumor; antibody response; ovary carcinoma; long term care; remission; ca 125 antigen; urinalysis; pemetrexed; adverse drug reaction; immunoglobulin g antibody; vaccine; immunoglobulin m antibody; conjugation; clinical outcome; international federation of gynecology and obstetrics; response evaluation criteria in solid tumors; klh; high grade serous ovarian carcinoma; humans; human; female; article; vaccines, combined; opt 821; absolute neutrophil count; treatment interruption; carcinoma, ovarian epithelial; short term survival; vaccine immunogenicity |
| Journal Title: | Cancer Immunology, Immunotherapy |
| Volume: | 72 |
| Issue: | 1 |
| ISSN: | 0340-7004 |
| Publisher: | Springer |
| Date Published: | 2023-01-01 |
| Start Page: | 183 |
| End Page: | 191 |
| Language: | English |
| DOI: | 10.1007/s00262-022-03225-1 |
| PUBMED: | 35779095 |
| PROVIDER: | scopus |
| PMCID: | PMC10123530 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Roisin O'Cearbhaill -- Export Date: 1 February 2023 -- Source: Scopus |
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