Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
- PMID: 38592381
- DOI: 10.1158/1078-0432.CCR-23-3639
Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Abstract
Purpose: We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator versus imiquimod plus a 9-valent human papillomavirus (HPV) vaccine (9vHPV) versus clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients.
Patients and methods: We randomly allocated 133 patients with untreated CIN2/3 in equal proportions to a 4-month treatment with self-applied vaginal suppositories containing imiquimod (Arm B) or imiquimod plus a 9vHPV (Arm C) versus clinical surveillance (Arm A). The main outcome was efficacy, defined as histologic regression to CIN1 or less. Secondary outcomes were HPV clearance and tolerability. Exploratory objectives included the comparison of cervical CD4/CD8 T-cell infiltration at baseline, mid-study, and posttreatment by flow cytometry among study arms.
Results: Of the 114 evaluable patients 77% and 23% harbored CIN2 and CIN3, respectively. Regression to CIN1 or less was observed in 95% of patients in the imiquimod group (Arm B) compared with 79% in the control/surveillance (Arm A); P = 0.043 and 84% in the imiquimod+9vHPV group (Arm C; P = 0.384 vs. Arm A). Neither of the treatment-arm differences from Arm A reached the prespecified α = 0.025 significance level. No significant differences were noted in the secondary outcome of rate of HPV clearance. The number of tissue-resident memory CD4/CD8 T cells in cytobrush samples demonstrated a >5-fold increase in Arm B/imiquimod when compared with Arm A/surveillance (P < 0.01). In contrast, there was no significant difference in T-cell responses among participants in Arm C when compared with Arm A. Imiquimod treatment was well tolerated.
Conclusions: Although imiquimod induced a higher regression to CIN1 or less and significant increases in CD4/CD8 T cells infiltrating the cervix, it did not meet its prespecified statistical outcome for efficacy. A higher regression rate than expected was observed in the surveillance arm of this prospective trial. Future clinical trials with imiquimod targeting CIN3 patients are warranted.
©2024 American Association for Cancer Research.
Similar articles
-
Treatment of cervical intraepithelial neoplasia with topical imiquimod: a randomized controlled trial.Obstet Gynecol. 2012 Jul;120(1):152-9. doi: 10.1097/AOG.0b013e31825bc6e8. Obstet Gynecol. 2012. PMID: 22914404 Clinical Trial.
-
Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors.Cochrane Database Syst Rev. 2018 May 9;5(5):CD009069. doi: 10.1002/14651858.CD009069.pub3. Cochrane Database Syst Rev. 2018. PMID: 29740819 Free PMC article. Review.
-
A Phase II, Prospective, Randomized, Multicenter, Open-Label Study of GX-188E, an HPV DNA Vaccine, in Patients with Cervical Intraepithelial Neoplasia 3.Clin Cancer Res. 2020 Apr 1;26(7):1616-1623. doi: 10.1158/1078-0432.CCR-19-1513. Epub 2019 Nov 14. Clin Cancer Res. 2020. PMID: 31727676 Clinical Trial.
-
Immunohistochemical analysis of CD4+ and CD8+ T-cell subsets in high risk human papillomavirus-associated pre-malignant and malignant lesions of the uterine cervix.Gynecol Oncol. 2006 Jul;102(1):22-31. doi: 10.1016/j.ygyno.2005.11.039. Epub 2006 Jan 20. Gynecol Oncol. 2006. PMID: 16427684
-
Imiquimod in cervical, vaginal and vulvar intraepithelial neoplasia: a review.Gynecol Oncol. 2015 Nov;139(2):377-84. doi: 10.1016/j.ygyno.2015.08.018. Epub 2015 Aug 31. Gynecol Oncol. 2015. PMID: 26335596 Review.