Treatment of Advanced Anal Cancer

Abstract

Metastatic anal squamous cell carcinoma, while relatively uncommon, is a difficult disease to treat. Lack of prospective data validating the toxicity and efficacy of various chemotherapeutic regimens has led to heterogeneous treatment of patients with this disease over time. Platinum-doublet chemotherapy, including regimens such as 5-fluorouracil (or capecitabine) and cisplatin, carboplatin and paclitaxel, or 5-fluorouracil, leucovorin, and oxaliplatin, remains a standard in the first-line setting for metastatic anal squamous cell carcinoma. Other systemic therapy options include single-agent regimens (irinotecan, paclitaxel, and others) or triplet chemotherapy (docetaxel, cisplatin, and fluorouracil or mitomycin, adriamycin, and cisplatin). As metastatic anal squamous cell carcinoma often harbors wild-type RAS, anti-epidermal growth factor receptor antibodies such as cetuximab and panitumumab have also been used. Checkpoint inhibitors such as nivolumab and pembrolizumab have demonstrated some efficacy in refractory metastatic anal squamous cell carcinoma. In oligometastatic disease, locoregional approaches after initial systemic therapy have seen some success in highly selected patients. Additional experimental options under investigation for the treatment of metastatic anal squamous cell carcinoma include adoptive T-cell transfer, vaccine therapy, and combinatorial therapy with chemotherapy, biologics, and/or immunotherapy.