https://scholars.lib.ntu.edu.tw/handle/123456789/557885
標題: | Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study | 作者: | CHIUN-SHENG HUANG Yu A.L. Tseng L.-M. Chow L.W.C. Hou M.-F. Hurvitz S.A. Schwab R.B. L Murray J. Chang H.-K. Chang H.-T. Chen S.-C. Kim S.-B. Hung J.-T. Ueng S.-H. Lee S.-H. Chen C.-C. Rugo H.S. |
關鍵字: | immunology; oncology; randomized trials | 公開日期: | 2020 | 出版社: | NLM (Medline) | 卷: | 8 | 期: | 2 | 來源出版物: | Journal for immunotherapy of cancer | 摘要: | PURPOSE: This randomized, double-blind, placebo-controlled, parallel-group, phase II trial assessed the efficacy and safety of adagloxad simolenin (OBI-822; a Globo H epitope covalently linked to keyhole limpet hemocyanin (KLH)) with adjuvant OBI-821 in metastatic breast cancer (MBC). METHODS: At 40 sites in Taiwan, USA, Korea, India, and Hong Kong, patients with MBC of any molecular subtype and ?2 prior progressive disease events with stable/responding disease after the last anticancer regimen were randomized (2:1) to adagloxad simolenin (AS/OBI-821) or placebo, subcutaneously for nine doses with low-dose cyclophosphamide. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, correlation of clinical outcome with humoral immune response and Globo H expression, and safety. RESULTS: Of 349 patients randomized, 348 received study drug. Patients with the following breast cancer subtypes were included: hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) (70.4%), triple negative (12.9%), and HER2+ (16.7%), similarly distributed between treatment arms. Median PFS was 7.6 months (95%?CI: 6.5-10.9) with AS/OBI-821 (n=224) and 9.2 months (95%?CI: 7.3-11.3) with placebo (n=124) (HR=0.96; 95%?CI: 0.74-1.25; p=0.77), with no difference by breast cancer subtype. AS/OBI-821 recipients with anti-Globo H IgG titer ?1:160 had significantly longer median PFS (11.1 months (95%?CI: 9.3-17.6)) versus those with titers <1:160 (5.5 months (95%?CI: 3.7-5.6); HR=0.52; p<0.0001) and placebo recipients (HR=0.71; p=0.03). Anti-KLH immune responses were similar at week 40 between AS/OBI-821 recipients with anti-Globo IgG titer ?1:160 and those with anti-Globo IgG titer <1:160. The most common adverse events with AS/OBI-821 were grade 1 or 2 injection site reactions (56.7%; placebo, 8.9%) and fever (20.1%; placebo, 6.5%). CONCLUSION: AS/OBI-821 did not improve PFS in patients with previously treated MBC. However, humoral immune response to Globo H correlated with improved PFS in AS/OBI-821 recipients, leading the way to further marker-driven studies. Treatment was well tolerated.NCT01516307. ? Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85088812874&doi=10.1136%2fjitc-2019-000342&partnerID=40&md5=a7e41f3b768d645f4f05808ef8670fc9 https://scholars.lib.ntu.edu.tw/handle/123456789/557885 |
ISSN: | 2051-1426 | DOI: | 10.1136/jitc-2019-000342 | SDG/關鍵字: | cancer vaccine; globo H-KLH vaccine; vaccine; adult; aged; breast tumor; clinical trial; controlled study; double blind procedure; female; human; metastasis; middle aged; mortality; phase 2 clinical trial; randomized controlled trial; survival analysis; treatment outcome; very elderly; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Cancer Vaccines; Double-Blind Method; Female; Humans; Middle Aged; Neoplasm Metastasis; Survival Analysis; Treatment Outcome; Vaccines, Conjugate |
顯示於: | 醫學系 |
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