Experimental and investigational drugs for the treatment of anal cancer

ABSTRACT

Introduction: Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy, but its incidence rates have been increasing in the last decade. Studies have demonstrated that up to 47% of patients with locally advanced disease have high-risk features for treatment failure. The potential high rates of recurrence after standard chemoradiotherapy for locally advanced disease and the lack of established care for metastatic disease have created an urgent need for the evaluation of new drugs that will ultimately improve the efficacy of treatment.

Areas covered: This review presents results of recent phase-I and -II clinical trials which evaluate novel therapeutic modalities. The review also describes the findings of comprehensive genomic profiling studies which provide insights for promising therapeutics.

Expert opinion: HPV vaccination is underutilized in the United States and as a result, HPV-associated malignancies are likely to continue for several decades; however, pivotal breakthroughs may create a foundation for distinctive treatment approaches for other HPV-associated malignancies for which no other standard of care exists

KEYWORDS:

• Anal cancer
• chemotherapy
• molecular targeted therapy
• immunotherapy
• precision medicine
• radiotherapy

Article Highlights

• Squamous cell carcinoma of the anal canal is a malignancy with rising incidence rates for the past decade.

• Concurrent chemoradiotherapy with curative intent is the cornerstone of the treatment for locally advanced disease. Nevertheless, it is associated with potential high rates of disease recurrence.

• The majority of cases are etiologically linked to HPV infection and its incidence is markedly elevated in immunocompromised patients.

• Comprehensive genomic profiling studies have consistently demonstrated that PIK3CA gene mutation is the most frequent genetic abnormality in the disease.

• EGFR inhibitors have failed in clinical trials owing to their elevated toxicity associated with combined modality therapy.

Novel trials including, molecular targeted therapy, immune checkpoint inhibitors, immunotherapeutic vaccines and adoptive T-cell therapy will be discussed.

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Declaration of interest

C. Eng has received research grants from Advaxis, Roche, and Forty Seven and has had Speaker’s Bureau Appointments with Roche, Bayer, Sirtex, and Merck. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.