Efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine in Chinese women aged 18-25 years: event-triggered analysis of a randomized controlled trial

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• 作者：Feng-cai Zhu ; Shang-Ying Hu ; Ying Hong ; Yue-Mei Hu ; Xun Zhang ; Yi-Ju Zhang ; Qin-Jing Pan ; Wen-Hua Zhang ; Fang-Hui Zhao ; Cheng-Fu Zhang ; Xiaoping Yang ; Jia-Xi Yu ; Jiahong Zhu ; Yejiang Zhu ; Feng Chen ; Qian Zhang ; Hong Wang ; Changrong Wang ; Jun Bi ; Shiyin Xue ; Lingling Shen ; Yan-Shu Zhang ; Yunkun He ; Haiwen Tang ; Naveen Karkada ; Pemmaraju Suryakiran ; Dan Bi and Frank Struyf
• 刊名：Cancer Medicine
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：6
• 期：1
• 页码：12-25
• 全文大小：401K
• ISSN：2045-7634

文摘

We previously reported the results of a phase II/III, double-blind, randomized controlled study in Chinese women (NCT00779766) showing a 94.2% (95% confidence interval: 62.7–99.9) HPV-16/18 AS04-adjuvanted vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 1 or higher (CIN1+) and/or 6-month (M) persistent infection (PI) with a mean follow-up of <2 years, and immunogenicity until 7 months post-dose 1. Here, we report efficacy and safety results from an event-triggered analysis with ~3 years longer follow-up, and immunogenicity until M24. Healthy 18–25-year-old women (N = 6051) were randomized (1:1) to receive three doses of HPV-16/18 vaccine or Al(OH)₃ (control) at M0, 1, 6. VE against HPV-16/18-associated CIN2+, and cross-protective VE against infections with nonvaccine oncogenic HPV types, immunogenicity, and safety were assessed. In the according-to-protocol efficacy cohort, in initially seronegative/DNA-negative women (vaccine group: N = 2524; control group: N = 2535), VE against HPV-16/18-associated CIN2+ was 87.3% (5.3–99.7); VE against incident infection or against 6-month persistent infection associated with HPV-31/33/45 was 50.1% (34.3–62.3) or 52.6% (24.5–70.9), respectively. At least, 99.6% of HPV-16/18-vaccines remained seropositive for anti-HPV-16/18 antibodies; anti-HPV-16 and -18 geometric mean titers were 1271.1 EU/mL (1135.8–1422.6) and 710.0 EU/ml (628.6–801.9), respectively. Serious adverse events were infrequent (1.7% vaccine group [N = 3026]; 2.5% control group [N = 3026]). Of the 1595 reported pregnancies, nine had congenital anomalies (five live infants, three elective terminations, one stillbirth) that were unlikely vaccination-related (blinded data). VE against HPV-16/18-associated CIN2+ was demonstrated and evidence of cross-protective VE against oncogenic HPV types was shown. The vaccine was immunogenic and had an acceptable safety profile.