Immunotherapy in advanced anal cancer: Is the beginning of a new era?

• Published in: Cancer treatment reviews 2022-04, Vol.105, p.102373-102373, Article 102373
• Main Authors: Ciardiello, Davide, Guerrera, Luigi Pio, Maiorano, Brigida Anna, Parente, Paola, Latiano, Tiziana Pia, Di Maio, Massimo, Ciardiello, Fortunato, Troiani, Teresa, Martinelli, Erika, Maiello, Evaristo
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Anus Neoplasms - therapy; Biomarkers; HIV Infections - drug therapy; HPV-related tumors; Humans; ICIs; Immunotherapy; Prospective Studies; Retrospective Studies; SCCA; Tumor Microenvironment
• ISSN: 0305-7372; 1532-1967
• DOI: 10.1016/j.ctrv.2022.102373

•Anal cancer is a rare disease that accounts for less than 3% of all gastrointestinal malignancies.•Squamous cell carcinoma of the anus (SCCA) represents the most frequent histologic variant: at least 90% of cases are associated with HPV infection.•Prognosis of patients with advanced/metastatic SCCA is poor.•After progression to first-line platinum-based chemotherapy, there is no established second-line treatment.•In this context, the use of immune checkpoint inhibitors (ICIs) demonstrated promising evidence of clinical activity in a subgroup of patients with pre-treated SCCA. For decades metastatic squamous cell carcinoma of the anus (SCCA)has been considered a rare disease with very limited treatment options and a dismal prognosis. Prior to 2017, no data from prospective studies on the management of metastatic SCCA were available with scant information from retrospective analyses and few treatment options. Recently, InterAAct trial showed an advantage of carboplatin plus paclitaxel over the historical standard of care represented by cisplatin plus 5-fluorouracil. Unfortunately, there is no established second-line treatment after progression to first-line platinum-based chemotherapy. Interestingly, a better understanding of the immunobiology of the neoplasm and the strict association between HPV/HIV infection and tumor microenvironment led to the development of immunotherapies. Emerging evidence suggests that the use of anti-PD1/PD-L1 agents could lead to promising antitumor activity in a subgroup of patients with pre-treated anal cancer, opening new therapeutic scenarios. Here, we will focus on completed clinical trials evaluating immunotherapy in patients with (SCCA), pointing out the future perspectives and possible biomarkers of response.