Progress in the treatment of anal cancer: an overview of the latest investigational drugs

ABSTRACT

Introduction

Anal cancer, a rare malignancy accounting for 2.5–3.0% of gastrointestinal cancers, primarily manifests as squamous cell carcinoma associated with HPV. Recent years have witnessed significant advancements in managing squamous cell carcinoma of the anus (SCCA), particularly with the introduction of immune checkpoint inhibitors (ICIs) and randomized data on front-line chemotherapy.

Areas covered

This review discusses the current standard treatments for both early and advanced SCCA, based on published data. The authors then describe the new approaches, focusing on ICI combinations, targeted agents, T-cell adoptive therapy, and HPV-therapeutic vaccines.

Expert opinion

The current standard treatment for SCCA includes front-line carboplatin and paclitaxel, with pembrolizumab and nivolumab as later-line options. While modified DCF has shown promise in single-arm studies, its role as a front-line therapy requires confirmation through randomized data. We eagerly anticipate the results of phase 3 trials investigating the front-line chemo-immunotherapy for metastatic SCCA and ICI consolidation following chemoradiation for early-stage SCCA. Novel approaches like T-cell adoptive therapy, HPV-therapeutic vaccines, and bifunctional antibodies combined with HPV vaccines are in early-stage trials for HPV-mediated tumors, including HPV-positive SCCA. These approaches targeting HPV epitopes may eventually gain tumor-agnostic approval, although their role in SCCA may take time to establish.

KEYWORDS:

• Anal cancer
• squamous cell carcinoma
• immunotherapy
• HPV therapeutic vaccines
• T-cell therapy

Article highlights

• Significant advancements in squamous cell carcinoma of the anus (SCCA) systemic therapy have been reported in recent years, particularly with randomized data on front-line chemotherapy and subsequent-line immune checkpoint inhibitors (ICIs).

• The current standard treatment for metastatic SCCA includes front-line carboplatin and paclitaxel, with later-line ICI monotherapy.

• While modified DCF has shown promise in single-arm studies, randomized data is needed for its front-line SCCA role.

• We anticipate phase 3 trial results for metastatic SCCA chemo-immunotherapy and ICI consolidation after chemoradiation for early-stage SCCA.

• Identifying better ICI predictive biomarkers in SCCA is imperative to potentially avoid cytotoxic chemotherapy.

• Early-stage trials are exploring T-cell adoptive therapy, HPV-therapeutic vaccines, and bifunctional antibodies with HPV vaccines for HPV-mediated tumors including SCCA.

Declaration of interest

R Kim has received consulting/advisory fees from AstraZeneca, Exelixis, Ipsen, Eisai, Roche, and Pfizer and Speakers Bureau fees from Incyte and AstraZeneca. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.