NEW YORK (Reuters Health) - Topical imiquimod works just as well as surgery for the first-line treatment of women with vulvar high-grade squamous intraepithelial lesions (vHSILs) — a precancerous lesion commonly caused by human papillomavirus (HPV).
That's according to results of the first randomized, non-inferiority trial comparing the two treatment approaches.
The study, conducted at six Austrian hospitals, included 110 patients with histologically confirmed p16 positive vHSIL, with 54 treated with imiquimod self-administered in escalating doses up to three times per week for four to six months and 53 to surgery (excision or ablation).
"We found that per-protocol treatment with imiquimod resulted in a complete clinical response rate of 80% at six months, compared with 79% after one surgical intervention," Dr. Gerda Trutnovsky of the Medical University of Graz, Austria, and colleagues report in The Lancet.
"Adverse events differed, with local pain being more intense after surgical treatment, and local pruritus and erythema being more common during imiquimod application," they note.
There were no between-group differences in health-related quality of life or treatment satisfaction. Invasive vulvar cancer was diagnosed in four patients at primary surgery and in no patients after complete imiquimod treatment.
For women with vHSIL, discussion of potential benefits and risks of treatment options is essential, the authors say.
Based on their results, "the oncological safety of imiquimod treatment can be assumed as long as regular clinical check-ups are carried out. Treatment decision should be guided by the comorbidities and preferences of patients," they write.
"A major drawback of imiquimod is the relatively long treatment period, which requires good patient compliance. In women asking for immediate treatment results and in suspected low treatment adherence, surgery might remain the treatment of choice. In all other women with vHSIL, imiquimod can be considered a first-line treatment option," the study team says.
The authors of linked comment note that this is the first study to "prove non-inferiority of imiquimod compared to surgery and confirms the high efficacy of imiquimod as a first-line treatment option for vHSIL."
"Although well executed, the major limitation of this study is the fact that the majority (78%) of patients included had a unifocal lesion, which does not represent the majority of patients with vHSIL," write Dr. Ekaterina Jordanova of the Netherlands Cancer Institute, in Amsterdam, and colleagues. Also, the average lesion size at baseline was smaller than in previous studies.
The comment authors agree that identifying women who are likely to derive the most benefit from imiquimod is important and gaining a better understanding of the drug's immune-modulating mechanism is essential for predicting clinical response.
They point to a recent study finding that complete clinical response to imiquimod is associated with coordinated influx of type-1 CD4 and CD8 T cells and CD14 inflammatory myeloid cells.
"Patients without such a pre-existent and coordinated immune microenvironment might show resistance to therapy. Therefore, further discovery of biomarkers to predict response is needed, using multiparameter methods such as spatial transcriptomics and imaging mass cytometry," Dr. Jordanova and co-authors conclude.
Funding for the study was provided by the Austrian Science Fund and Austrian Gynecological Oncology Group. The study investigators and comment authors have declared no competing interests.
SOURCE: https://bit.ly/3rVaLYk and https://bit.ly/3LmrwTH The Lancet, online April 25, 2022.
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