Abstract
Simple SummaryThis is an exciting moment in clinical research in the squamous cell carcinoma of the anus (SCCA). Historical barriers regarding this disease are vanishing thanks to the creation of research networks in this rare pathology, gained knowledge in tumor biology and its environment in this human papillomavirus (HPV)-induced disease in more than 90% of patients, and the arrival of taxane-based chemotherapy regimens as well as immunotherapies and its novel combinations. This review sheds light on the present and the future of research on SCCA, new understanding of its rational for ongoing clinical trials, with special focus in locally advanced and metastatic diseases.Squamous cell carcinoma of the anus is an orphan disease, and after more than three decades of no substantial advances in disease knowledge and treatment, it is finally gaining momentum with the arrival of a taxane-based chemotherapy and immunotherapy. Currently, about 20 combination clinical trials with an anti-PD1/L1 are ongoing in localized and advanced stages, in association with radiotherapy, chemotherapy, tumor vaccines, anti-CTLA4, anti-EGFR, or antiangiogenic molecules. Moreover, a new biomarker with high sensitivity and specificity such as HPV circulating tumor DNA (HPV ctDNA) by liquid biopsy, is improving not only the prognostic measurement but also the treatment strategy guidance for this disease. Finally, better understanding of potential targets is reshaping the present and future clinical research in this unique, HPV genotype-16-related disease in the great majority of patients.
Highlights
We describe the recent progress and ongoing clinical trials in squamous cell carcinoma of the anus (SCCA)
Along with the high complete response rate, these findings suggest the potential use of DCF in neoadjuvant/adjuvant setting [16]
Immune biomarker data of Epitopes-HPV01 and -HPV02 trials showed that DCF is a good backbone chemotherapy to combine with anti-PD1/L1 since it increases antitumor human telomerase immunity and decreases Myeloid-derived suppressor cells (MDSC), two major factors significantly correlated with prognosis [10,24]
Summary
About a third of patients experience recurrence with a progressionfree survival (PFS) rate at 5 years less than 70% based on phase III trials. Most patients included in these trials assessing chemoradiotherapy were at an early stage (I and II), and the recurrence rate is even higher in patients with a locally advanced disease. A pooled analysis of updated data of 115 patients in Epitopes-HPV01 and 02 trials demonstrated a long-lasting complete response in 25%. The InterAACT “pick the winner” randomized phase II trial evaluated two doublet regimens: carboplatin plus paclitaxel (CP), and cisplatin plus 5-fluorouracil (CP) Both regimens had similar efficacy (ORR of 59% and 57% including 13% and 17% of complete responses, respectively) and toxicity profiles (grade III/IV toxicity rate of 71 and 76%, respectively) and failed to demonstrate its prespecified main endpoints [11]. We describe the recent progress and ongoing clinical trials in SCCA
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